Hydrochloric Acid → 3-{1-[4-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-3-hydroxymethyl-butyryl]-piperidin-4-yl}1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one

HRID 1795048Notes

Reaction equation

HRID 1795048 reaction equation
[NH2:1][C:2]1[C:33]([C:34]([F:37])([F:36])[F:35])=[CH:32][C:5]([CH2:6][CH:7]([CH2:11][C:12](=[O:31])[N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)[C:8](O)=[O:9])=[CH:4][C:3]=1[Cl:38].C1N=CN(C(N2C=NC=C2)=O)C=1.[BH4-].[Na+].Cl>C1COCC1.O>[NH2:1][C:2]1[C:33]([C:34]([F:35])([F:36])[F:37])=[CH:32][C:5]([CH2:6][CH:7]([CH2:8][OH:9])[CH2:11][C:12]([N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)=[O:31])=[CH:4][C:3]=1[Cl:38]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 221846012-(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]-butyric Acid2×

Product 1

HCID 221845953-{1-[4-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-3-hydroxymethyl-butyryl]-piperidin-4-yl}1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3.00 g (5.425 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]-butyric acid (Intermediate product 68) in 100 mL THF was added 1.054 g (6.500 mmol) CDI and the mixture was stirred for 2 hours at RT. This solution was added dropwise under a nitrogen atmosphere over 5 minutes to an ice-cooled solution of 0.728 g (19.250 mmol) sodium borohydride in 50 mL water and the mixture was stirred for 16 hours at RT. The reaction mixture was acid ified with 1 N aqueous HCl to pH 2 and exhaustively extracted with EtOAc. The combined org. phases were washed with sat. aqueous NaCl solution, dried over sodium sulphate and evaporated i. vac.

Workup

  1. stirringthe mixture was stirred for 16 hours at RT
  2. extractionexhaustively extracted with EtOAc
  3. washphases were washed with sat. aqueous NaCl solution
  4. dry with materialdried over sodium sulphate
  5. customevaporated i

Sources & evidence

ORD record
ord-5ce44fe6c952441a86bf08d20bf6c8cd
Source dataset
uspto-grants-2006_04
Patent number
US07026312B2

Reaction notes

Loading…