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

HRID 1896094Notes

Reaction equation

HRID 1896094 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[F:31][C:32]([F:43])([F:42])[C:33]1[N:37]2[CH2:38][CH2:39][NH:40][CH2:41][C:36]2=[CH:35][N:34]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>ClCCl>[O:13]=[C:11]([N:40]1[CH2:39][CH2:38][N:37]2[C:33]([C:32]([F:43])([F:31])[F:42])=[N:34][CH:35]=[C:36]2[CH2:41]1)[CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23]

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 341763145,6,7,8-Tetrahydro-3-(trifluoromethyl)imidazo[1,5-a]pyrazine

Product 1

HCID 57518397(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamic acid tert-butyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyric acid 1f (8.6 g, 45 mmol) and 9.4 mL of triethylamine were dissolved in 300 mL of dichloromethane. After stirring for 5 minutes, 3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine 1k (15.0 g, 45 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (17.1 g, 67.3 mmol) were added to the solution successively. The reaction mixture was reacted for 2 hours and then concentrated under reduced pressure. The resulting residues were purified by silica gel column chromatography with system B as eluant to obtain the title compound tert-Butyl (R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamate 1m (20.0 g, yield 88%) as a white solid. 1H NMR (400 MHz, CD3OD, ppm): δ 7.25 (m, 1H), 7.11 (m, 1H), 7.032 (s, 1H), 4.93 (m, 2H), 4.35 (m, 3H), 4.05 (m, 2H), 2.99 (m, 2H), 2.73 (m, 2H), 1.34 (s, 9H).

Workup

  1. customThe reaction mixture was reacted for 2 hours
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting residues were purified by silica gel column chromatography with system B as eluant

Sources & evidence

ORD record
ord-38dcf3f2a9784303bdf3ac5642ebf991
Source dataset
uspto-grants-2013_08
Patent number
US08518946B2

Reaction notes

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