Methylamine hydrochloride → (R)-N-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)-2-(trifluoromethyl)pyrrolidine-1-sulfonamide

HRID 1969643Notes

Reaction equation

HRID 1969643 reaction equation
[CH3:1][C@H:2]1[C@@H:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([S:19]([C:22]5[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=5)(=[O:21])=[O:20])[C:13]=4[N:14]=[CH:15][C:10]3=[CH:9][N:8]=2)[CH2:5][C@@H:4]([NH:29][S:30](N2CCOC2=O)(=[O:32])=[O:31])[CH2:3]1.Cl.CN.C(N[C@@H]1C[C@H](C(O)=O)[C@H](C)C1)(=O)C.[F:55][C:56]([F:63])([F:62])[C@H:57]1[CH2:61][CH2:60][CH2:59][NH:58]1>CC#N>[CH3:1][C@H:2]1[C@@H:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([S:19]([C:22]5[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=5)(=[O:20])=[O:21])[C:13]=4[N:14]=[CH:15][C:10]3=[CH:9][N:8]=2)[CH2:5][C@@H:4]([NH:29][S:30]([N:58]2[CH2:59][CH2:60][CH2:61][C@@H:57]2[C:56]([F:63])([F:62])[F:55])(=[O:32])=[O:31])[CH2:3]1

Participants

6

Reactant 4

HCID 6364545Methylamine hydrochlorideHCID 7015082(2R)-2-(Trifluoromethyl)pyrrolidineHCID 67997884N-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)-2-oxooxazolidine-3-sulfonamideHCID 67998106(1S,2R,4S)-4-acetamido-2-methylcyclopentanecarboxylic acid

Product 1

HCID 67998165(R)-N-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)-2-(trifluoromethyl)pyrrolidine-1-sulfonamideYield 75.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)-2-oxooxazolidine-3-sulfonamide (0.200 g, 0.261 mmol, prepared from 5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride (WO2009152133) and (1S,2R,4S)-4-acetamido-2-methylcyclopentanecarboxylic acid [prepared from ethyl 4-amino-2-methyl-cyclopentanecarboxylate (WO2009152133) using G, AA, and Z] using H, OO, BB, and ZZ) and (R)-2-trifluoromethylpyrrolidine (0.055 g, 0.392 mmol) in MeCN (1.4 mL) was added TEA (0.073 mL, 0.523 mmol). The reaction was irradiated in a CEM microwave at about 120° C. for about 0.5 h. The reaction mixture was cooled to ambient temperature and concd under reduced pressure to afford a residue. The crude material was purified by silica gel chromatography eluting with a gradient of 0-70% EtOAc in DCM to afford (R)-N-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)-2-(trifluoromethyl)pyrrolidine-1-sulfonamide (0.12 g, 75%, 72% purity) as an off-white solid: LC/MS (Table 1, Method a) Rt=2.79 min; MS m/z: 611 (M+H)+.

Workup

  1. customThe reaction was irradiated in a CEM microwave at about 120° C. for about 0.5 h
  2. customconcd under reduced pressure to afford a residue
  3. customThe crude material was purified by silica gel chromatography
  4. washeluting with a gradient of 0-70% EtOAc in DCM

Sources & evidence

ORD record
ord-47f64954a27b40b992b4e89d747e4b34
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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