2-(4-Amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyraldehyde → 3-(1-{4-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(3-dimethylamino-2,2-dimethyl-propyl)-1h-benzimidazol-2-yl]-butyryl}-piperidin-4-yl)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one

HRID 1795060노트

반응식

HRID 1795060 반응식
[NH2:1][C:2]1[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][C:5]([CH2:6][CH:7]([CH2:10][C:11](=[O:30])[N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:29])[CH2:14][CH2:13]2)[CH:8]=O)=[CH:4][C:3]=1[Cl:37].Cl.Cl.Cl.[CH3:41][N:42]([CH3:56])[CH2:43][C:44]([CH3:55])([CH3:54])[CH2:45][NH:46][C:47]1[C:48]([NH2:53])=[CH:49][CH:50]=[CH:51][CH:52]=1>CN(C=O)C>[NH2:1][C:2]1[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][C:5]([CH2:6][CH:7]([C:8]2[N:46]([CH2:45][C:44]([CH3:55])([CH3:54])[CH2:43][N:42]([CH3:41])[CH3:56])[C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[N:53]=2)[CH2:10][C:11]([N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:29])[CH2:16][CH2:17]2)=[O:30])=[CH:4][C:3]=1[Cl:37]

참가 물질

4

반응물 2

HCID 221845352-(4-Amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyraldehyde2회HCID 22184559n-(3-Dimethylamino-2,2-dimethyl-propyl)-benzene-1,2-diamine-trihydrochloride2회

생성물 1

HCID 101972343-(1-{4-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(3-dimethylamino-2,2-dimethyl-propyl)-1h-benzimidazol-2-yl]-butyryl}-piperidin-4-yl)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 320 mg (0.596 mmol) 2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyraldehyde (Intermediate product 36) in 7 mL DMF was added 230 mg (0.695 mmol) N-(3-dimethylamino-2,2-dimethyl-propyl)-benzene-1,2-diamine-trihydrochloride (Intermediate product 37) and the mixture was stirred for 16 hours in an atmosphere of air. The reaction mixture was evaporated down i. vac. and the residue combined with EtOAc. The org. phase was washed with sat. aqueous sodium bicarbonate solution, dried over sodium sulphate and evaporated i. vac. The crude product was purified by column chromatography (silica gel, gradient dichloromethane/MeOH 20/1→10/1 v/v) then (Alox, neutral, activity II-III, gradient EtOAc/MeOH 100/0→40/1) and HPLC-MS (Zorbax Bonus C18 amide-phase 5 μm, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v).

후처리

  1. customThe reaction mixture was evaporated down i
  2. washphase was washed with sat. aqueous sodium bicarbonate solution
  3. dry with materialdried over sodium sulphate
  4. customevaporated i
  5. customThe crude product was purified by column chromatography (silica gel, gradient dichloromethane/MeOH 20/1→10/1 v/v)

출처 및 근거

ORD 기록
ord-191b5612f1e14799a7701feb5f3b0125
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07026312B2

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