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 494755Notes

Reaction equation

HRID 494755 reaction equation
[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]

Participants

4

Reactant 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]-butyraldehyde2×HCID 22184559n-(3-Dimethylamino-2,2-dimethyl-propyl)-benzene-1,2-diamine-trihydrochloride2×

Product 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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 III-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).

Workup

  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)

Sources & evidence

ORD record
ord-989a159a3e1f42e4827673eb3b8828e6
Source dataset
uspto-grants-2009_05
Patent number
US07538115B2

Reaction notes

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