Triethylamine → (R)-[3-(1-acetyl-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 1895643Notes

Reaction equation

HRID 1895643 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[N:7]2[CH2:8][CH2:9][NH:10][CH2:11][C:6]2=[C:5]([C:12](=[O:14])[CH3:13])[N:4]=1.[C:17]([O:21][C:22]([NH:24][C@H:25]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])[CH2:26][C:27](O)=[O:28])=[O:23])([CH3:20])([CH3:19])[CH3:18].C(N(CC)CC)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>ClCCl>[C:17]([O:21][C:22](=[O:23])[NH:24][C@H:25]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])[CH2:26][C:27]([N:10]1[CH2:9][CH2:8][N:7]2[C:3]([C:2]([F:1])([F:15])[F:16])=[N:4][C:5]([C:12](=[O:14])[CH3:13])=[C:6]2[CH2:11]1)=[O:28])([CH3:20])([CH3:18])[CH3:19]

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 57518456Ethanone,1-[5,6,7,8-tetrahydro-3-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-

Product 1

HCID 57518457(R)-[3-(1-acetyl-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 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(3-Trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-1-yl)-ethanone 27g (192 mg, 0.72 mmol) and (R)-3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyric acid 1f (0.24 g, 0.72 mmol) were dissolved in 20 mL of dichloromethane under stirring, and triethylamine (0.4 mL, 2.88 mmol) was then added to the solution. After stirring to mix well, bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.275 g, 1.08 mmol) was then added. The reaction mixture was reacted overnight at room temperature 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-acetyl-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 27h (0.3 g) as a white solid.

Workup

  1. stirringAfter stirring
  2. additionto mix well
  3. customThe reaction mixture was reacted overnight at room temperature
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9623d318551d45fc890eae678a712ee4
Source dataset
uspto-grants-2013_08
Patent number
US08513411B2

Reaction notes

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