benzyl 4-(1-{(S)-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]-butyryl}-piperidin-4-yl)-piperazin-1-carboxylate → (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butan-1,4-dione

HRID 736946Notes

Reaction equation

HRID 736946 reaction equation
[NH2:1][C:2]1[C:54]([C:55]([F:58])([F:57])[F:56])=[CH:53][C:5]([CH2:6][C@@H:7]([CH2:32][C:33](=[O:52])[N:34]2[CH2:39][CH2:38][CH:37]([N:40]3[CH2:46][CH2:45][C:44]4[CH:47]=[CH:48][CH:49]=[CH:50][C:43]=4[NH:42][C:41]3=[O:51])[CH2:36][CH2:35]2)[C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:21][CH2:20][N:19](C(OCC4C=CC=CC=4)=O)[CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[Cl:59]>[Ni].CO>[NH2:1][C:2]1[C:54]([C:55]([F:57])([F:56])[F:58])=[CH:53][C:5]([CH2:6][C@@H:7]([CH2:32][C:33]([N:34]2[CH2:35][CH2:36][CH:37]([N:40]3[CH2:46][CH2:45][C:44]4[CH:47]=[CH:48][CH:49]=[CH:50][C:43]=4[NH:42][C:41]3=[O:51])[CH2:38][CH2:39]2)=[O:52])[C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[Cl:59]

Participants

4

Reactant 1

HCID 68591073benzyl 4-(1-{(S)-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]-butyryl}-piperidin-4-yl)-piperazin-1-carboxylate

Product 1

HCID 57848411(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butan-1,4-dione

Reagents, catalysts & solvents 2

HCID 935NickelCatalyst2×HCID 887MethanolSolvent

Procedure

100 mg Raney nickel were added to a solution of 250 mg (0.30 mmol) benzyl 4-(1-{(S)-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]-butyryl}-piperidin-4-yl)-piperazin-1-carboxylate in 30 mL MeOH and the reaction mixture was stirred for 5 h at RT and 50 psi H2. To complete the reaction another 100 mg of Raney nickel were added and the mixture was stirred for a further 10 h at RT. The catalyst was suction filtered, the solvent eliminated i. vac. and the residue purified by HPLC.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred for a further 10 h at RT
  3. filtrationfiltered
  4. customand the residue purified by HPLC

Sources & evidence

ORD record
ord-6d0badaa00874021a72cd23255e64e12
Source dataset
uspto-grants-2009_09
Patent number
US07595312B2

Reaction notes

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