Dimethylformamide → 2,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole-3-carbonitrile

HRID 1189553Notes

Reaction equation

[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[S:15]([N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)(=[O:17])=[O:16].[CH3:23][N:24](C=O)C>C(#N)C>[CH3:7][C:5]1[NH:4][C:3]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)(=[O:17])=[O:16])=[C:2]([CH3:1])[C:6]=1[C:23]#[N:24]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 3,5-dimethyl-2-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole (576.0 mg, 1.809 mmol) and N-chlorosulfonylisocyanide (197 μl, 2.261 mmol) in acetonitrile (9.0 ml) was stirred at 25° C. for 1 hour. DMF (140 μl, 1.809 mmol) was then added and the resulting mixture was stirred for an additional 16 hours. It was quenched with water (100 ml) and extracted with dichloromethane (100 ml×2). The organic layers were combined, filtered, and evaporated to give an oil. The oil was purified by column chromatography (0 to 70% ethyl acetate in hexanes) to give 2,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole-3-carbonitrile (513.6 mg, 1.495 mmol, 83% yield) as brown oil. 1H NMR (CDCl3/400 MHz) δ (ppm) 9.10 (bs, 1H), 7.82-7.77 (m, 1H), 7.46-7.40 (m, 1H), 7.30-7.23 (m, 2H), 4.10 (s, 2H), 3.33-3.27 (m, 4H), 2.20 (s, 3H), 2.18 (s, 3H), 1.92-1.88 (m, 4H). MS m/z: 344.3 (M+1).

Workup

stirringthe resulting mixture was stirred for an additional 16 hours
customIt was quenched with water (100 ml)
extractionextracted with dichloromethane (100 ml×2)
filtrationfiltered
customevaporated
customto give an oil
customThe oil was purified by column chromatography (0 to 70% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-e3ec5a4e907d4f1b830f23656e540c3c
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08674115B2

Reaction notes

Loading…