Triethylamine → HCID 59548956, compound

HRID 1895616Notes

Reaction equation

HRID 1895616 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]([OH:24])=[O:23])=[C:15]2[CH2:14]1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:40][CH2:41][C:42]([O:44][CH3:45])=[O:43].C(N(CC)CC)C.O=C1N([ClH:59]P([ClH]N2CCOC2=O)=O)CCO1>ClCCl>[ClH:59].[CH3:45][O:44][C:42](=[O:43])[CH2:41][NH:40][C:22]([C:21]1[N:20]=[C:19]([C:25]([F:26])([F:27])[F:28])[N:16]2[CH2:17][CH2:18][N:13]([C:11](=[O:12])[CH2:10][C@H:9]([NH2:8])[CH2:29][C:30]3[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=3[F:38])[CH2:14][C:15]=12)=[O:24].[CH3:45][O:44][C:42](=[O:43])[CH2:41][NH:40][C:22]([C:21]1[N:20]=[C:19]([C:25]([F:27])([F:28])[F:26])[N:16]2[CH2:17][CH2:18][N:13]([C:11](=[O:12])[CH2:10][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:29][C:30]3[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=3[F:38])[CH2:14][C:15]=12)=[O:23]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 122755Glycine methyl ester 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 2

HCID 44194134(R)-({7-[3-Amino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carbonyl}-amino)-acetic acid methyl ester hydrochlorideHCID 59548956HCID 59548956, compoundYield 107.3%

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 (150 mg, 0.27 mmol) and methyl glycinate hydrochloride (512 mg, 0.408 mmol) were dissolved in 8 mL of dichloromethane under stirring, and triethylamine (0.25 mL, 1.62 mmol) was then added to the solution. After stirring for 5 minutes, bis(2-oxo-3-oxazolidinyl)phosphonic chloride (0.138 g, 0.54 mmol) was added. The reaction mixture was reacted at room temperature for 20 hours 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]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carbonyl}-amino)-acetic acid methyl ester 16a (90 mg, yield 53.6%) as a light yellow oil.

Workup

  1. stirringAfter stirring for 5 minutes
  2. customThe reaction mixture was reacted at room temperature for 20 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-bdaeef327cb041aa8c09a53f97239956
Source dataset
uspto-grants-2013_08
Patent number
US08513411B2

Reaction notes

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