Synthesis of α-Sulfoximino Tetrazoles via Azido-Ugi Four-Component Reaction

Abstract

The sulfoximine-based tetrazoles have been synthesized via azido-Ugi four-component reactions of sulfoximines, isocyanides, aldehydes, and TMS-azide in MeOH at 70 °C in the presence of InCl₃. Replacement of sulfoximines with sulfonimidamides (SIA) has delivered the corresponding SIA-based tetrazole. Interestingly, SIA also acts as a surrogate amine to furnish the corresponding aminotetrazole as a by-product.

Key words

sulfoximines - sulfonimidamides - Ugi reaction - tetrazoles - isocyanides

Tetrazoles are of great importance due to their distinctive chemical and biological properties.[1] This moiety has found applications in fields such as medicine,[2] biochemistry,[3] pharmacology,[4] materials,[5] coordination chemistry,[6] and organocatalysis[7] (Figure [1]), as well as in synthetic chemistry.[8] Importantly, tetrazoles are well-established bioisosteres of carboxylic acids.[9]

Figure 1 Representative tetrazole-bearing derivatives used in various fields

Sulfoximines have recently received very good attention in synthetic, medicinal, and agrochemical areas.[10] Sulfoximine-containing bioactive molecules include Atuveciclib, BAY 1251152, and AZD6738.[11] Additionally, sulfoximines have been used as chiral auxiliaries and ligands in asymmetric synthesis, and as directing groups in ortho-C–H functionalization.[12] Considering the importance of tetrazoles, together with our recent interest in sulfoximines[13] and related chemistry,[14] we herein report that sulfoximine-based tetrazoles, i.e., α-sulfoximino tetrazoles, have been prepared via four-component reaction of sulfoximines, isocyanides, aldehydes, and TMS-N₃.

The classical four-component Ugi reaction utilizes carboxylic acids as one of the nucleophiles to synthesize the bis-amide.[15] Replacement of the carboxylic acid with an azide delivers the corresponding tetrazole in the Azido-Ugi tetrazole reaction (UT-4CR) (Scheme [1a]). UT-4CRs have been widely employed to construct diverse tetrazole-based systems by altering the substituents in the substrate.[16] However, most of the previous reports on UT- 4CRs employ sp³-hybridized primary or secondary amines as amine component. Hence, despite being a very well-established field, the reaction behavior with sp² hybridized imine nucleophiles remains to be studied. In this context, we employed sulfoximines, which contain the sp²-hybridized imino group, as nucleophile in the UT-4CR to synthesize α-sulfoximino tetrazoles (Scheme [1b]).

Scheme 1 Schematic representation of (a) general and (b) current UT-4CR

Previously, Bolm et al. prepared N-(1H)-tetrazole sulfoximines via a ZnBr_2–catalyzed cycloaddition reaction (Scheme [2a]).[17] Recently, the same research group prepared 2-sulfoximidoyl acetic acids via Petasis reaction (Scheme [2b]).[18] Our α-sulfoximino tetrazoles can be considered as tetrazole isosteres of 2-sulfoximidoyl acetic acid (Scheme [2b]).

Scheme 2 Previous routes to (a) sulfoximine derived tetrazoles, (b) α-sulfoximidoyl acetic acids (this work: isosteric replacement of -COOH with tetrazole to access α-sulfoximino tetrazole).

The starting NH-sulfoximines were prepared by following the reported protocol.[19a] We initiated the investigations with a four-component reaction of sulfoximine 1a, p-tolualdehyde (2a), t-butyl isocyanide (3a), and TMS-N₃ (4) under conditions that are summarized in Table [1]. Initially, the reaction mixture was stirred in methanol at room temperature for 24 h, but the desired tetrazole 5a was obtained only in 10% yield, along with unreacted sulfoximine and aldehyde (entry 1). To obtain a better outcome, the Lewis acid ZnCl₂ was added as mediator and a 40% yield of 5a was isolated (entry 2). Increased temperature gave a better yield of 5a (entries 3 and 4), and replacement of ZnCl₂ with InCl₃ resulted in a further improved yield at 70 °C (entry 6). Other Lewis acids such as Cu(OTf)₂, CuBr, and Zn(OTf)₂ were not as effective as InCl₃ at 70 °C (entries 6–9). Other solvents, including EtOH, CH₃CN, DCE, toluene, and DCM were investigated (entries 10–14), but MeOH was found to be the best solvent for the transformation. When we replaced the TMS-N₃ in the reaction with NaN₃ we could isolate only 41% of 5a (entry 15). It should be noted that the Lewis acids were needed in 50 mol%; the use of lesser amounts (5/10/20/30/40 mol%) InCl₃ led to diminished product formation along with isolation of unreacted starting sulfoximine and aldehyde. A higher amount of InCl₃ (60%) did not give a better outcome.

Table 1 Optimization of the Synthesis of Sulfoximine Derived Tetrazoles^a

Entry	Solvent	Lewis acid	Temp (°C)	Time (h)	Yield (%)b
1c	MeOH	–	r.t.	24	10
2c	MeOH	ZnCl2	r.t.	15	40
3	MeOH	ZnCl2	45	12	46
4	MeOH	ZnCl2	70	12	50
5	MeOH	InCl3	45	12	55
6	MeOH	InCl3	70	12	61
7	MeOH	Cu(OTf)2	70	12	20
8	MeOH	CuBr	70	12	NR
9	MeOH	Zn(OTf)2	70	12	54
10	EtOH	InCl3	70	12	36
11	CH3CN	InCl3	70	12	21
12	DCE	InCl3	70	12	NR
13	Toluene	InCl3	70	12	12
14	DCM	InCl3	70	12	26
15d	MeOH	InCl3	45	12	41

^a General conditions for the one-pot four-component reaction: 1a (1.2 equiv), 2a (1.2 equiv), 3a (1.0 equiv), 4 (1.0 equiv), Lewis acid (0.5 equiv) in 1 mL solvent unless otherwise stated.

^b Isolated yield.

^c 1:1:1:1 ratio of all substrates.

^d NaN₃ was used instead of TMSN₃.

With the optimal reaction condition in hand, next we explored the scope and limitations of the method for the synthesis of sulfoximine based tetrazoles 5. Differently substituted sulfoximines, aldehydes, and isocyanides were utilized, and the results are shown in Scheme [3]. Various aromatic aldehydes with electron-poor and electron-rich substitution patterns underwent successful reaction. It was noted that electron-deficient aryl aldehydes provided better outcomes than their electron-rich counterparts. Bulky triphenylamine aldehyde and heteroaromatic benzothiophene aldehyde also delivered 5n–p in good yields. Several cyclic and acyclic isocyanides such as cyclohexyl, adamantyl, and t-butyl isocyanide furnished the desire products in moderate to good yields. Unfortunately, the primary alkyl isocyanide (p-toluenesulfonylmethyl isocyanide) and aromatic isocyanide (4-methoxyphenyl isocyanide) both failed to produce the desired products 5s and 5t. The modifications of the S-aryl group (phenyl to substituted phenyl) and S-alkyl group (methyl to ethyl) of the NH-sulfoximines were well tolerated in the conversion.

In addition to S-aryl S-alkyl sulfoximines, diaryl/dialkyl symmetrical sulfoximines underwent reaction smoothly to produce the corresponding products 5q–r. The electronic effects induced by S-aryl substituents appeared to have only a minor influence on product formation.

Scheme 3 Substrate scope for preparing sulfoximine-based tetrazoles

All the synthesized compounds were characterized by ¹H and ¹³C NMR spectroscopy, and HRMS, and structures were unambiguously confirmed by single-crystal XRD analysis of two representative compounds (5c and 5e; see the Supporting Information).

The successful utilization of NH-sulfoximines as nucleophiles in the UT-4CR, inspired us to apply sulfonimidamide (SIA) (6) (Scheme [4]) to construct SIA derived tetrazoles via UT-4CR. SIAs, the mono-aza analogues of sulfonamides, with a stereogenic tetrahedral sulfur atom and sp² hybridized imino group (free -NH), are considered an important emerging scaffold due to their applications in asymmetric synthesis and the medicinal and agrochemical industries.[20]

Initially, SIA (6a) was treated with aldehyde 2a, isocyanide 3a, and TMS-N₃ (4) under the previously optimized reaction conditions (Table [1], entry 6), but the desired product 7a was formed in only minor amounts, accompanied by the side-product, cyclic amine-based tetrazole 8a as the major product. SIA 6 would appear to be acting as surrogate amine to yield 8. A previous report from our group had already described the surrogate nature of SIA under specific conditions.[14a] Considering that the elevated reaction temperatures may result in S–N bond cleavage, the reaction was performed at lower temperature (Table [2], entry 3) and 7a was obtained as the major product (52%) at 45 °C, along with 18% of by-product 8a. Screening of other Lewis acids, such as ZnCl₂ and Zn(OTf)₂ showed that they were not as effective as InCl₃ (entries 4 and 5).

Table 2 Optimization of the Synthesis of Sulfonimidamide Derived Tetrazoles^a

Entry	Conditions				Yield (%)b
	Solvent	Lewis acid	Temp (°C)	Time (h)	7a	8a
1	MeOH	InCl3	70	10	18	65
2	MeOH	InCl3	r.t	10	0	20
3	MeOH	InCl3	45	10	52	18
4	MeOH	ZnCl2	45	10	30	40
5	MeOH	ZnCl2	45	10	34	38

^a Conditions for the one-pot four-component reaction: 6a (1.2 equiv), 2a (1.2 equiv), 3a (1.0 equiv), 4 (1.0 equiv), Lewis acid (0.5 equiv), in 1 mL solvent.

^b Isolated yield.

Hence, by following the optimized condition (Table [2], entry 3), we scrutinized the scope and generality of the reaction with SIA (Scheme [5]). Reaction of SIAs with various S-aryl (-Ph, 4-MePh, 4-OMePh) and S-cyclic amines (pyrrolidine and piperidine) worked equally well to deliver the corresponding product 7. Diverse substituted aromatic aldehydes, with electron-withdrawing and -donating substituents were employed successfully. The bulky triphenylamine benzaldehyde readily took part in the reaction to furnish 7e. Different secondary and tertiary isocyanides were also well tolerated to deliver the desired products in moderate yield. However, our attempts to use a primary alkyl isocyanide (p-toluenesulfonyl methyl isocyanide) and an aromatic isocyanide (4-methoxyphenyl isocyanide) were unsuccessful (7i–j).

Scheme 4 Synthesis of sulfonimidamide derived tetrazole

Scheme 5 Substrate scope for sulfonimidamide based tetrazoles

A probable mechanistic approach based on previous literature reports[21] and the current findings is portrayed in Scheme [6]. In the presence of InCl₃, sulfoximine 1 reacts with aldehyde 2 to generate 5Ia, which, on reaction with the isocyanide, yields intermediate nitrilium cation 5Ib. Subsequent cycloaddition of 5Ib with azide delivers the expected product 5 via 5Ic. SIA 6 follows a similar route to furnish the corresponding tetrazole 7. However, the surrogate nature of the SIA, which leads to 8, can be explained as in Scheme [7]. In the presence of InCl₃, the sp³ amine of SIA attacks the aldehyde to generate intermediate 8Ia, which undergoes intramolecular rearrangement (transacylation) and C–O bond cleavage of 8Ib to produced iminium intermediate 8Ic via elimination. Successive reaction of isocyanide with 8Ic and further [3+2] cycloaddition of 8Id with azide leads to the formation of 8.

In conclusion, we have demonstrated the azido-Ugi four-component reaction for the synthesis of α-sulfoximino tetrazoles. A wide range of sulfoximines, aldehydes, and isocyanides have been assembled with TMS-azide in the presence of InCl₃ to form two new C–N bonds, one C–C bond, and one N–N bond in a single process. Use of SIAs instead of sulfoximines has delivered the corresponding SIA based tetrazoles. These compounds can be considered as sulfoximine/SIA-derived tetrazole isosteres of α-amino acids. Notably, SIAs can also act as surrogate amines to produce the corresponding aminotetrazoles as by-products.

Scheme 6 Plausible mechanism for the formation of the UT product

Scheme 7 Proposed mechanism for the formation of cyclic amine-based tetrazole 8

The starting sulfoximines/sulfonimidamides were synthesized by following reported methods.[19] The aldehydes, isocyanides, TMSN₃, InCl₃, and MeOH were purchased from various suppliers and used as received. ¹H and ¹³C NMR spectra were recorded with a Bruker spectrometer operating at 500 and 125 MHz, respectively, in CDCl₃ or CD₆CO­ as solvents. Mass spectra were recorded with an Agilent QTOF G6545 XT spectrometer at 50,000 resolutions using ESI mode. Melting points are uncorrected.

Sulfoximine Synthesis; General Procedure

To a stirred solution of diaryl (or alkylaryl) sulfide (1 mmol) in MeOH (5 mL), NH₄CO₂NH₂ (1.5 equiv) and PhI(OAc)₂ (2.3 equiv) were added, and the solution was stirred at r.t. for 3–4 h. After the disappearance of the sulfide (checked by TLC), the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (25–40% EtOAc/hexane).

For the gram-scale reaction, sulfide (20 mmol) and MeOH (100 mL) were used.

One-Pot Tandem Synthesis of Tetrazole Based Sulfoximine/Sulfonimidamide (5/7); General Procedure

Precautions: We have not experienced any problems with the use of TMSN₃ under the reaction conditions employed and working on small scale. However, essential precautions should be taken on scaling up this chemistry.

A solution of sulfoximine (30 mg 1.2 equiv), aldehyde (1.2 equiv), isocyanide (1.0 equiv), and InCl₃ (0.5 equiv) in MeOH (1 mL) in a 20 mL sealed tube was stirred at 70 °C under argon atmosphere. After 15 min, TMS-azide (1.0 equiv) was added to the reaction mixture and the reaction was stirred for the stipulated period. Upon completion of reaction (confirmed by TLC), the reaction mixture was poured in water and extracted with EtOAc (2 × 10 mL). The organic layers were washed with sat. aq. NaHCO₃, water, brine and dried over anhydrous Na₂SO₄. After filtration, the solvent was evaporated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography with 20–30% of EtOAc in hexane as the eluent.

For sulfonimidamides, the reaction was stirred at 45 °C.

All the synthesized compounds (except 5q/5r) have more than one (generally two) stereogenic centers. Hence, mixtures of diastereomers could be expected to form. However, we isolated only single diastereomer for 5a–m, 5p, 5q, and 7. Another diastereomer was formed in trace amounts for 5a–m, 5p, 5q, and 7. For compounds 5n–o, two diastereomers were isolated in almost equal amounts.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(p-tolyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5a)

Colorless viscous liquid; 61% yield. TLC (SiO₂): R_f 0.25 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.63 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.01 (s, 1 H), 3.08 (s, 3 H), 2.29 (s, 3 H), 1.41 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.2, 139.9, 138.9, 137.7, 137.4, 132.7, 130.2, 129.4, 127.5, 61.7, 52.3, 45.6, 29.9, 21.1.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₀H₂₅BrN₅OS: 462.0958; found: 462.0960.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(phenyl)methyl) S-Methyl S-p-Tolyl Sulfoximine (5b)

Yellowish viscous liquid; 60% yield. TLC (SiO₂): R_f 0.26 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.65 (d, J = 7.0 Hz, 1 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.32 (d, J = 7.5 Hz, 1 H), 7.27–7.24 (m, 2 H), 7.19 (d, J = 8.0 Hz, 2 H), 7.05 (t, J = 8.0 Hz, 1 H), 6.01 (s, 1 H), 3.06 (s, 3 H), 2.34 (s, 3 H), 1.36 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.3, 144.5, 140.8, 137.5, 136.5, 130.1, 128.7, 127.5, 123.6, 61.7, 52.6, 45.6, 29.9, 21.6.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₀H₂₆N₅OS: 384.1853; found: 384.1857.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5c)

White solid; mp 114–116 °C; 65% yield. TLC (SiO₂): R_f 0.35 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.58 (br s, 4 H), 7.28–7.27 (m, 4 H), 6.00 (s, 1 H), 3.12 (s, 3 H), 1.42 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.8, 139.9, 139.1, 138.5, 133.8, 132.8, 130.1, 128.9, 128.9, 61.9, 52.0, 45.6, 29.8.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₉H₂₂BrClN₅OS: 482.0411; found: 482.0418.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(p-tolyl)methyl) S-Methyl S-4-Chlorophenyl Sulfoximine (5d)

Yellowish viscous liquid; 57% yield. TLC (SiO₂): R_f 0.21 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.71 (d, J = 8.5 Hz, 2 H), 7.41 (d, J = 8.5 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 6.01 (s, 1 H), 3.08 (s, 3 H), 2.29 (s, 3 H), 1.41 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.3, 139.9, 138.4, 137.7, 137.5, 130.1, 129.7, 129.5, 127.5, 61.7, 52.4, 45.7, 29.9, 21.1.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₀H₂₅ClN₅OS: 418.1463; found: 418.1472.

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5e)

White solid; mp 117–118 °C; 68% yield. TLC (SiO₂): R_f 0.45 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.67 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 5.91 (s, 1 H), 4.51–4.46 (m, 1 H), 3.18 (s, 3 H), 2.25–2.24 (m, 2 H), 1.96–1.93 (m, 2 H), 1.81–1.76 (m, 2 H), 1.49–1.46 (m, 2 H), 1.32–1.30 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.2, 140.6, 138.1, 137.2, 133.9, 133.1, 130.1, 128.8, 128.0, 58.3, 51.5, 45.5, 33.2, 25.5, 24.9.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₁H₂₄BrClN₅OS: 508.0568; found: 508.0571.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Ethyl S-Phenyl Sulfoximine (5f)

White solid; mp 120–122 °C; 62% yield. TLC (SiO₂): R_f 0.25 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.67 (dd, J = 8.0, 1.0 Hz, 2 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.29–7.26 (m, 4 H), 6.06 (s, 1 H), 3.34–3.19 (m, 2 H), 1.41 (s, 9 H), 1.26 (t, J = 8.0 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.1, 139.9, 139.7, 137.7, 133.5, 129.5, 129.4, 128.9, 128.7, 61.8, 51.8, 51.4, 30.0, 7.1.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₀H₂₅ClN₅OS: 418.1463; found: 418.1473.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Ethyl S-4-Methoxyphenyl Sulfoximine (5g)

White solid; mp 129–130 °C; 67% yield. TLC (SiO₂): R_f 0.21 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.56 (d, J = 9.0 Hz, 2 H), 7.31–7.25 (m, 4 H), 6.90 (d, J = 9.0 Hz, 2 H), 6.09 (s, 1 H), 3.84 (s, 3 H), 3.29–3.17 (m, 2 H), 1.45 (s, 9 H), 1.25 (t, J = 7.5 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 163.6, 156.1, 139.8, 133.3, 131.4, 128.7, 128.5, 128.3, 114.6, 61.8, 55.6, 51.7, 51.6, 29.9, 7.1.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₁H₂₇ClN₅O₂S: 448.1568; found: 448.1578.

N-((1-Adamantyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Ethyl S-Phenyl Sulfoximine (5h)

White solid; mp 132–134 °C; 66% yield. TLC (SiO₂): R_f 0.25 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.66 (d, J = 8.5 Hz, 2 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.31–7.26 (m, 4 H), 6.08 (s, 1 H), 3.33–3.21 (m, 2 H), 2.07–2.01 (m, 6 H), 1.94–1.92 (m, 3 H), 1.67–1.64 (m, 3 H), 1.60–1.57 (m, 3 H), 1.27 (t, J = 7.5 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.1, 140.0, 137.9, 133.5, 133.4, 129.4, 129.3, 128.9, 128.7, 62.9, 51.9, 51.4, 42.1, 35.6, 29.6, 7.1.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₆H₃₁ClN₅OS: 496.1932; found: 496.1935.

N-((1-Adamantyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Methyl S-4-Methoxyphenyl Sulfoximine (5i)

White solid; mp 179–181 °C; 70% yield. TLC (SiO₂): R_f 0.24 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.63 (d, J = 9.0 Hz, 2 H), 7.29 (q, J = 8.5 Hz, 4 H), 6.91 (d, J = 9.0 Hz, 2 H), 6.04 (s, 1 H), 3.84 (s, 3 H), 3.14 (s, 3 H), 2.08–2.04 (m, 6 H), 1.98–1.96 (m, 3 H), 1.68–1.65 (m, 3 H), 1.61–1.59 (m, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 163.7, 156.1, 139.8, 133.5, 130.8, 130.5, 128.9, 128.7, 114.7, 63.0, 55.8, 52.2, 46.0, 42.0, 35.6, 29.6.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₆H₃₀ClN₅NaO₂S: 534.1701; found: 534.1711.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(2-bromophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5j)

White solid; mp 125–127 °C; 57% yield. TLC (SiO₂): R_f 0.25 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.75 (dd, J = 8.0, 1.5 Hz, 1 H), 7.69 (d, J = 8.5 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.50 (dd, J = 8.0, 1.0 Hz, 1 H), 7.27 (td, J = 7.5, 1.0 Hz, 1 H), 7.10 (td, J = 7.5, 1.5 Hz, 1 H), 6.39 (s, 1 H), 2.94 (s, 3 H), 1.46 (s, 9 H).

¹³C NMR (126 MHz, CDCl₃): δ = 155.6, 139.2, 133.3, 132.5, 131.1, 129.9, 129.8, 128.6, 128.2, 125.2, 123.2, 61.7, 51.6, 46.0, 29.8.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₉H₂₂Br₂N₅OS: 525.9901; found: 525.9912.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(3-bromophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5k)

Colorless viscous liquid; 62% yield. TLC (SiO₂): R_f 0.25 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.67 (d, J = 2.0 Hz, 1 H), 7.53 (brs, 4 H), 7.34–7.32 (m, 1 H), 7.17–7.16 (m, 1 H), 7.11 (t, J = 8.0 Hz, 1 H), 5.96 (s, 1 H), 3.07 (s, 3 H), 1.38 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.6, 142.8, 139.9, 138.5, 132.8, 131.1, 130.6, 130.2, 130.1, 126.1, 122.9, 62.0, 52.0, 45.7, 29.9.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₉H₂₂Br₂N₅OS: 525.9906; found: 525. 9889.

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(3-bromophenyl)methyl) S-Ethyl S-4-Methoxyphenyl Sulfoximine (5l)

Colorless viscous liquid; 68% yield. TLC (SiO₂): R_f 0.21 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.65 (s, 1 H), 7.47 (d, J = 9.0 Hz, 2 H), 7.30 (dt, J = 7.5, 1.5, 0.5 Hz, 1 H), 7.23 (dt, J = 7.5, 1.5, 0.5 Hz, 1 H), 7.09 (t, J = 8.0 Hz, 1 H), 6.91 (d, J = 9.0 Hz, 2 H), 5.91 (s, 1 H), 4.49–4.46 (m, 1 H), 3.80 (s, 3 H), 3.22–3.16 (m, 2 H), 2.21–2.18 (m, 1 H), 2.01–1.98 (m, 1 H), 1.94–1.92 (m, 1 H), 1.87–1.84 (m, 1 H), 1.78–1.71 (m, 1 H), 1.55–1.53 (m, 1 H), 1.31–1.26 (m, 1 H), 1.23 (t, J = 7.5 Hz, 3 H), 1.18–1.14 (m, 1 H), 1.01–0.98 (d, J = 13.1 Hz, 1 H), 0.90–0.88 (d, J = 12.4 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 163.9, 155.4, 142.5, 140.5, 131.4, 130.7, 129.9, 126.8, 125.3, 122.7, 114.9, 58.8, 58.1, 55.7, 51.2, 33.1, 25.5, 24.8, 7.5.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₃H₂₉BrN₅O₂S: 518.1220; found: 518.1229.

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-bromophenyl)methyl) S-Ethyl S-2-Thiophenyl Sulfoximine (5m)

Brownish viscous liquid; 67% yield. TLC (SiO₂): R_f 0.30 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.69 (d, J = 6.5 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.32 (d, J = 3.5 Hz, 1 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.12–7.10 (m, 1 H), 6.11 (s, 1 H), 4.50–4.47 (m, 1 H), 3.38–3.36 (m, 2 H), 2.26–2.23 (m, 2 H), 1.95–1.92 (m, 3 H), 1.81–1.76 (m, 2 H), 1.73–1.71 (m, 1 H), 1.48–1.45 (m, 2 H), 1.37 (t, J = 7.0 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.2, 140.7, 138.9, 137.5, 135.3, 131.6, 128.5, 128.3, 121.8, 58.9, 53.3, 51.1, 33.2, 25.5, 24.9, 7.9.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₀H₂₅BrN₅OS₂: 494.0678; found: 494.0671.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(N,N-diphenylaniline)methyl) S-methyl S-4-Methoxyphenyl Sulfoximine (5n)

Obtained as a diastereomeric mixture. Total yield 72%.

Diastereomer 1

White solid; mp 170–172 °C. TLC (SiO₂): R_f 0.24 (40% EtOAc in hexane).

IR (KBr): 3059, 3038, 2937, 2835, 1735, 1587, 1508, 1487, 1405, 1375, 1317, 1259, 1215, 1154, 1078, 1025, 981, 800, 697 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.66 (d, J = 9.0 Hz, 2 H), 7.22 (t, J = 8.0 Hz, 6 H), 7.04 (dd, J = 7.5 Hz, 4 H), 7.00–6.98 (m, 4 H), 6.89 (d, J = 9.0 Hz, 2 H), 6.02 (s, 1 H), 3.83 (s, 3 H), 3.12 (s, 3 H), 1.46 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 163.5, 156.5, 147.6, 147.1, 134.6, 130.8, 130.7, 129.2, 128.4, 124.3, 123.5, 122.9, 114.5, 61.6, 55.7, 51.9, 45.9, 29.9.

HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₃₂H₃₄N₆NaO₂S: 589.2356; found: 589.2356.

Diastereomer 2

White solid; mp 172–173 °C.

¹H NMR (500 MHz, CDCl₃): δ = 7.71 (d, J = 9.0 Hz, 2 H), 7.23–7.17 (m, 6 H), 7.01–6.99 (m, 2 H), 6.97–6.95 (m, 4 H), 6.92 (d, J = 9.0 Hz, 2 H), 6.83 (d, J = 8.5 Hz, 2 H), 6.02 (s, 1 H), 3.87 (s, 3 H), 3.10 (s, 3 H), 1.68 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 163.1, 157.0, 147.5, 147.1, 133.2, 130.3, 129.2, 128.9, 125.4, 124.3, 123.1, 122.9, 114.3, 61.5, 55.6, 52.5, 46.3, 30.1.

HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₃₂H₃₄N₆NaO₂S: 589.2356; found: 589.2357.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(N,N-diphenylaniline)methyl)S-Methyl S-Phenyl Sulfoximine (5o)

Obtained as a diastereomeric mixture. Total yield 70%.

Diastereomer 1

White solid; mp 169–170 °C. TLC (SiO₂): R_f 0.26 (40% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.76 (d, J = 7.5 Hz, 2 H), 7.54 (t, J = 7.5 Hz, 1 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.24–7.20 (m, 6 H), 7.04 (d, J = 7.5 Hz, 4 H), 7.00–6.97 (m, 4 H), 6.01 (s, 1 H), 3.14 (s, 3 H), 1.43 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.4, 147.7, 147.3, 139.9, 134.5, 133.4, 129.5, 129.3, 128.6, 128.5, 124.5, 123.6, 123.0, 61.6, 52.0, 45.6, 30.0.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₃₁H₃₂N₆NaOS: 559.2251; found: 559.2257.

Diastereomer 2

White solid; mp 167–168 °C.

¹H NMR (500 MHz, CDCl₃): δ = 7.79 (d, J = 7.5 Hz, 2 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.45 (t, J = 8.0 Hz, 2 H), 7.23–7.19 (m, 4 H), 7.17 (d, J = 8.5 Hz, 2 H), 7.00 (t, J = 7.5 Hz, 2 H), 6.95 (d, J = 7.5 Hz, 4 H), 6.80 (d, J = 8.5 Hz, 2 H), 6.04 (s, 1 H), 3.13 (s, 3 H), 1.68 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 157.0, 147.6, 140.2, 132.9, 129.7, 129.3, 129.2, 129.1, 128.3, 127.2, 124.4, 123.3, 123.0, 61.7, 52.7, 46.1, 30.3.

HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₃₁H₃₂N₆NaOS: 559.2251; found: 559.2259.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(benzo[b]thiophen-3-yl)methyl) S-Ethyl S-4-Methoxyphenyl Sulfoximine (5p)

Brown viscous liquid; 58% yield. TLC (SiO₂): R_f 0.18 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.18 (d, J = 8.0 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.66 (d, J = 9.0 Hz, 2 H), 7.43–7.34 (m, 2 H), 7.20 (s, 1 H), 6.87 (d, J = 9.0 Hz, 2 H), 6.46 (s, 1 H), 3.83 (s, 3 H), 3.29–3.22 (m, 1 H), 3.18–3.13 (m, 1 H), 1.34 (s, 9 H), 1.20 (t, J = 7.5 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 163.4, 156.1, 140.9, 137.2, 134.9, 131.4, 129.0, 125.7, 124.5, 124.3, 122.7, 122.3, 114.3, 61.2, 55.6, 51.7, 46.4, 29.6, 6.8.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₃H₂₈N₅O₂S₂: 470.1679; found: 470.1689.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-bromophenyl)methyl) S-Diisopropyl Sulfoximine (5q)

Off-white solid; mp 87–88 °C; 44% yield. TLC (SiO₂): R_f 0.20 (30% EtOAc in hexane).

IR (KBr): 3343, 2997, 2981, 2879, 2136, 1907, 1673, 1586, 1511, 1484, 1460, 1393, 1314, 1297, 1261, 1251, 1147, 1127, 1042, 1009, 950, 829, 783, 665 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.42 (d, J = 8.5 Hz, 2 H), 7.26 (d, J = 8.5 Hz, 2 H), 6.32 (s, 1 H), 3.35–3.31 (m, 2 H), 1.62 (s, 9 H), 1.30 (d, 7.0 Hz,3 H), 1.28 (d, J = 6.5 Hz, 3 H), 1.21 (d, 7.0 Hz, 3 H), 1.18 (d, 7.0 Hz, 3 H),

¹³C NMR (125 MHz, CDCl₃): δ = 156.9, 141.3, 131.5, 129.1, 121.4, 61.9, 52.7, 51.8, 51.0, 30.1, 16.1, 15.7, 15.5, 15.4.

HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₁₈H₂₈BrN₅NaOS: 442.1271; found: 442.1273.

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) Di-S-4-methoxyphenyl Sulfoximine (5r)

Yellowish viscous liquid; 47% yield. TLC (SiO₂): R_f 0.28 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.87 (d, J = 9.0 Hz, 2 H), 7.62 (d, J = 9.0 Hz, 2 H), 7.53 (d, J = 9.0 Hz, 2 H), 7.38 (d, J = 8.5 Hz, 2 H), 6.95 (d, J = 6.5 Hz, 2 H), 6.85 (d, J = 9.0 Hz, 2 H), 4.60 (s, 1 H), 4.30–4.27 (m, 1 H), 3.83 (s, 3 H), 3.81 (s, 3 H), 1.98–1.95 (m, 2 H), 1.83–1.79 (m, 1 H), 1.60–1.56 (m, 3 H), 1.34–1.31 (m, 2 H), 1.19 (br s, 2 H).

¹³C NMR (125 MHz, CDCl₃): δ = 171.5, 163.3, 163.2, 133.0, 132.2, 130.6, 130.4, 128.7, 128.4, 127.0, 114.9, 114.7, 114.6, 61.8, 58.9, 55.8, 48.0, 33.1, 25.7, 24.8.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₈H₃₁ClN₅O₃S: 552.1831; found: 552.1840.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(p-tolyl)methyl) S-Pyrrolidyl S-Phenyl Sulfonimidamide (7a)

Yellowish solid; mp 110–112 °C; 52% yield. TLC (SiO₂): R_f 0.45 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.97 (d, J = 7.5 Hz, 2 H), 7.57–7.54 (m, 1 H), 7.51–7.48 (m, 2 H), 7.45 (d, J = 7.5 Hz, 2 H), 7.14 (d, J = 7.5 Hz, 2 H), 6.53 (s, 1 H), 3.09–3.07 (m, 2 H), 2.96–2.94 (m, 2 H), 2.33 (s, 3 H), 1.72 (brs, 4 H), 1.59 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 157.1, 137.9, 137.2, 136.7, 132.4, 129.1, 128.9, 127.8, 127.4, 61.9, 51.1, 48.4, 30.2, 25.2, 21.2.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₃H₃₁N₆OS: 439.2275; found: 439.2281.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Pyrrolidyl S-Phenyl Sulfonimidamide (7b)

Off-white solid; mp 107–108 °C; 56% yield. TLC (SiO₂): R_f 0.45 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.94 (d, J = 8.0 Hz, 2 H), 7.54–7.51 (m, 5 H), 7.31 (d, J = 8.0 Hz, 2 H), 6.52 (s, 1 H), 3.09–3.08 (m, 2 H), 2.95–2.93 (m, 2 H), 1.72 (brs, 4 H), 1.59 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.6, 139.5, 136.5, 133.5, 132.6, 129.1, 128.9, 128.7, 127.8, 62.2, 50.9, 48.5, 30.2, 25.2.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₂H₂₈ClN₆OS: 459.1728; found: 459.1733.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-bromophenyl)methyl) S-Pyrrolidyl S-p-Tolyl Sulfonimidamide (7c)

White solid; mp 89–91 °C; 59% yield. TLC (SiO₂): R_f 0.44 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.80 (d, J = 8.0 Hz, 2 H), 7.45 (brs, 4 H), 7.29 (d, J = 8.0 Hz, 2 H), 6.48 (s, 1 H), 3.08–3.06 (m, 2 H), 2.93–2.91 (m, 2 H), 2.41 (s, 3 H), 1.71 (brs, 4 H), 1.58 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 156.6, 143.4, 140.2, 133.5, 131.5, 129.6, 129.2, 127.8, 121.5, 62.2, 51.0, 48.4, 30.2, 25.2, 21.5.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₃H₃₀BrN₆OS: 517.1380; found: 517.1385.

N-((1-Adamantyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Pyrrolidyl S-4-Methoxyphenyl Sulfonimidamide (7d)

White solid; mp 83–95 °C; 61% yield. TLC (SiO₂): R_f 0.42 (30% EtOAc in hexane).

IR (KBr): 3357, 3259, 3085, 2960, 2839, 2581, 2037, 1898, 1727, 1590, 1494, 1390, 1325, 1261, 1154, 1098, 1059, 1017, 892, 833, 753, 677 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.87 (d, J = 9.0 Hz, 2 H), 7.50 (d, J = 8.0 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H), 6.97 (d, J = 9.0 Hz, 2 H), 6.50 (s, 1 H), 3.86 (s, 3 H), 3.09–3.07 (m, 2 H), 2.96–2.94 (m, 2 H), 2.31–2.28 (m, 3 H), 2.21–2.19 (m, 4 H), 2.11 (br s, 4 H), 1.64–1.61 (m, 8 H).

¹³C NMR (125 MHz, CDCl₃): δ = 162.8, 156.6, 139.8, 133.2, 129.9, 128.8, 128.4, 128.3, 114.0, 63.0, 55.5, 51.2, 48.3, 41.9, 35.6, 29.6, 25.1.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₉H₃₆ClN₆O₂S: 567.2303; found: 567.2307.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(N,N-diphenylaniline)methyl)S-Pyrrolidyl S-p-Tolyl Sulfonimidamide (7e)

Yellow solid; mp 189–191 °C; 58% yield. TLC (SiO₂): R_f 0.45 (30% EtOAc in hexane).

IR (KBr): 3033, 2972, 2849, 1588, 1504, 1485, 1402, 1317, 1272, 1254, 1194, 1006, 789, 754, 699 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.82 (d, J = 8.0 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.24–7.21 (m, 4 H), 7.05–7.04 (m, 5 H), 7.02–6.98 (m, 3 H), 6.48 (s, 1 H), 3.10–3.06 (m, 2 H), 2.98–2.93 (m, 2 H), 2.41 (s, 3 H), 1.65 (s, 9 H), 1.63–1.61 (m, 4 H).

¹³C NMR (125 MHz, CDCl₃): δ = 157.1, 147.8, 147.2, 143.1, 135.0, 133.8, 129.5, 129.3, 128.6, 127.9, 124.4, 123.6, 123.0, 61.9, 51.1, 48.4, 30.3, 25.2, 21.5.

HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₃₅H₃₉N₇NaOS: 628.2829; found: 628.2825.

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Piperidyl S-p-Tolyl Sulfonimidamide (7f)

Yellowish solid; mp 112–113 °C; 55% yield. TLC (SiO₂): R_f 0.44 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 7.74 (d, J = 8.0 Hz, 2 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.35–7.32 (m, 4 H), 6.23 (s, 1 H), 4.72–4.67 (m, 1 H), 2.90–2.85 (m, 2 H), 2.80–2.76 (m, 2 H), 2.44 (s, 3 H), 1.99–1.97 (m, 1 H), 1.93–1.87 (m, 1 H), 1.76–1.74 (m, 1 H), 1.68–1.66 (m, 5 H), 1.49–1.47 (m, 2 H), 1.42–1.39 (m, 2 H), 1.33–1.25 (m, 3 H), 1.18–1.16 (m, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.7, 143.4, 138.7, 133.7, 132.7, 129.7, 128.8, 128.4, 127.7, 58.0, 49.8, 47.7, 32.4, 25.5, 25.3, 25.0, 23.6, 21.6.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₆H₃₄ClN₆OS: 513.2198; found: 513.2193.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Piperidyl-S-4-Methoxyphenyl Sulfonimidamide (7g)

Yellowish viscous liquid; 57% yield. TLC (SiO₂): R_f 0.42 (30% EtOAc in hexane).

¹H NMR (500 MHz, acetone-d ₆): δ = 7.84 (d, J = 9.0 Hz, 2 H), 7.69 (d, J = 8.5 Hz, 2 H), 7.39 (d, J = 8.5 Hz, 2 H), 7.09 (d, J = 9.0 Hz, 2 H), 6.45 (s, 1 H), 3.87 (s, 3 H), 2.78–2.77 (m, 4 H), 1.67 (s, 9 H), 1.43–1.39 (m, 4 H), 1.33–1.31 (m, 2 H).

¹³C NMR (125 MHz, Acetone): δ = 163.9, 157.6, 141.6, 133.6, 130.7, 130.2, 129.2, 128.1, 114.9, 62.5, 56.1, 51.3, 48.3, 25.9, 24.2.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₄H₃₂ClN₆O₂S: 503.1990; found: 503.2001.

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(2-bromophenyl)methyl) S-Piperidyl S-4-Bromophenyl Sulfonimidamide (7h)

Yellowish viscous liquid; 45% yield. TLC (SiO₂): R_f 0.44 (30% EtOAc in hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.11 (dd, J = 8.0, 1.5 Hz, 1 H), 7.74 (d, J = 8.5 Hz, 2 H), 7.64 (d, J = 8.5 Hz, 2 H), 7.54 (dd, J = 8.0, 1.0 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.22–7.18 (m, 1 H), 6.52 (s, 1 H), 4.79–4.73 (m, 1 H), 2.82–2.79 (m, 2 H), 2.67–2.62 (m, 2 H), 1.99–1.88 (m, 5 H), 1.81–1.78 (m, 1 H), 1.71–1.69 (m, 1 H), 1.37–1.32 (m, 3 H), 1.29–1.25 (m, 3 H), 1.21–1.18 (m, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.0, 139.5, 134.5, 132.7, 132.2, 131.3, 129.7, 129.2, 128.1, 127.7, 122.8, 57.8, 48.8, 48.0, 33.1, 32.8, 25.6, 25.4, 25.2, 23.5.

HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₅H₃₁Br₂N₆OS: 621.0641; found: 621.0644.

Conflict of Interest

The authors declare no conflict of interest.

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Publication History

Received: 12 October 2022

Accepted after revision: 17 November 2022

Accepted Manuscript online:
17 November 2022

Article published online:
12 December 2022