Triethylamine → (R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-8-methyl-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester

HRID 221509Notes

Reaction equation

HRID 221509 reaction equation
Cl.[CH3:2][O:3][C:4]([C:6]1[N:7]=[C:8]([C:16]([F:19])([F:18])[F:17])[N:9]2[CH2:14][CH2:13][NH:12][CH:11]([CH3:15])[C:10]=12)=[O:5].[C:20]([O:24][C:25]([NH:27][C@H:28]([CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42])[CH2:29][C:30](O)=[O:31])=[O:26])([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>ClCCl>[CH3:2][O:3][C:4]([C:6]1[N:7]=[C:8]([C:16]([F:19])([F:18])[F:17])[N:9]2[CH2:14][CH2:13][N:12]([C:30](=[O:31])[CH2:29][CH:28]([NH:27][C:25]([O:24][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:26])[CH2:33][C:34]3[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=3[F:42])[C@H:11]([CH3:15])[C:10]=12)=[O:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidHCID 684212988-Methyl-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester hydrochloride

Product 1

HCID 57518482(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-8-methyl-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl esterYield 77.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

8-Methyl-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester hydrochloride 39c crude product (0.289 g, 0.96 mmol) and (R)-3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyric acid if (0.353 g, 1.06 mmol) were dissolved in 10 mL of dichloromethane, followed by addition of triethylamine (0.4 mL, 2.9 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.368 g, 1.45 mmol) under stirring. The reaction mixture was stirred 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)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-8-methyl-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester 39d (0.43 g, yield 77.2%) as a yellow oil.

Workup

  1. stirringThe reaction mixture was stirred 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-b215ff9eb4d4433d8ab0a3c3c0886a29
Source dataset
uspto-grants-2012_06
Patent number
US08207161B2

Reaction notes

Loading…