Triethylamine → (R)-[3-[1-(1,1-dioxo-thiomorpholine-4-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 221439

反応式

HRID 221439 の反応式
[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].Cl.[NH:40]1[CH2:45][CH2:44][S:43](=[O:47])(=[O:46])[CH2:42][CH2:41]1.O=C1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[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:28])([F:26])[F:27])=[N:20][C:21]([C:22]([N:40]3[CH2:45][CH2:44][S:43](=[O:47])(=[O:46])[CH2:42][CH2:41]3)=[O:23])=[C:15]2[CH2:14]1)=[O:12])([CH3:2])([CH3:4])[CH3:3]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 12324096Thiomorpholine 1,1-dioxide 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

生成物 1

HCID 57518412(R)-[3-[1-(1,1-dioxo-thiomorpholine-4-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収率 94.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

(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), thiomorpholine-1,1-dioxide hydrochloride (73 mg, 0.54 mmol), bis(2-oxo-3-oxazolidinyl)phosphonic chloride (0.138 g, 0.54 mmol) and triethylamine (0.25 mL, 1.62 mmol) were dissolved in 8 mL of dichloromethane under stirring, and 4 mL of N,N-dimethylformamide was then added to the solution. 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-(1,1-dioxo-thiomorpholine-4-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 6a (170 mg, yield 94%) as a white solid.

後処理

  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

出典と根拠

ORDレコード
ord-a0794d539d6e462793894e18550abd64
出典データセット
uspto-grants-2012_06
特許番号
US08207161B2

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