Triethylamine → (R)-[3-[1-((S)-3-fluoro-pyrrolidine-1-carbonyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl]-3-oxo-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester

HRID 1895635Notes

Reaction equation

HRID 1895635 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH2:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]2[C:19]([C:25]([F:28])([F:27])[F:26])=[N:20][C:21]([C:22](O)=[O:23])=[C:15]2[CH2:14]1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C.Cl.[F:62][C@H:63]1[CH2:67][CH2:66][NH:65][CH2:64]1>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH2:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]2[C:19]([C:25]([F:26])([F:28])[F:27])=[N:20][C:21]([C:22]([N:65]3[CH2:66][CH2:67][C@H:63]([F:62])[CH2:64]3)=[O:23])=[C:15]2[CH2:14]1)=[O:12])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 16217739(s)-3-Fluoropyrrolidine hydrochlorideHCID 59548952(R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid

Product 1

HCID 57518449(R)-[3-[1-((S)-3-fluoro-pyrrolidine-1-carbonyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl]-3-oxo-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl esterYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid 2a (0.15 g, 0.27 mmol), bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.140 g, 0.54 mmol), triethylamine (0.4 mL, 2.6 mmol) and (S)-3-fluoropyrrolidine hydrochloride (68 mg, 0.54 mmol) were dissolved in 10 mL of dichloromethane under stirring. The reaction mixture was reacted at room temperature overnight and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (R)-[3-[1-((S)-3-fluoro-pyrrolidine-1-carbonyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl]-3-oxo-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester 26a (0.15 g, yield 89%) as a white solid.

Workup

  1. customThe reaction mixture was reacted at room temperature overnight
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-20857d7a0df841a3abba473734b140fe
Source dataset
uspto-grants-2013_08
Patent number
US08513411B2

Reaction notes

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