4-(Aminomethyl)benzonitrile → (7aS,6S)-4-{[2-(3,5-dichloro-phenyl)-1,3-dioxo-hexahydro-pyrrolo[1,2-c]imidazol-6-ylamino]-methyl}-benzonitrile

HRID 49985

Reaction equation

HRID 49985 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@H:12]3[CH2:15][C:16](=O)[CH2:17][N:11]3[C:10]2=[O:19])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:20]([C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH2:27])=[CH:24][CH:23]=1)#[N:21].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@H:12]3[CH2:15][C@H:16]([NH:27][CH2:26][C:25]4[CH:28]=[CH:29][C:22]([C:20]#[N:21])=[CH:23][CH:24]=4)[CH2:17][N:11]3[C:10]2=[O:19])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 826084-(Aminomethyl)benzonitrileHCID 5049666Sodium triacetoxyborohydrideHCID 21301015(7aS)-2-(3,5-dichloro-phenyl)-tetrahydro-pyrrolo[1,2-c]imidazole-1,3,6-trione

Product 1

HCID 21300996(7aS,6S)-4-{[2-(3,5-dichloro-phenyl)-1,3-dioxo-hexahydro-pyrrolo[1,2-c]imidazol-6-ylamino]-methyl}-benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound of formula (In), wherein R11 is 4-cyano, m is 1, W=NH, and the bonds depicted as wavy bonds define the 7aS,6S stereoisomer, was prepared as follows. To a solution of (7aS)-2-(3,5-dichloro-phenyl)-tetrahydro-pyrrolo[1,2-c]imidazole-1,3,6-trione (0.5 g) (0.0017 mol) (Preparation 20), in 50 mL of DCM was added molecular sieves 4A, 4-cyanobenzyl amine (0.27 g) (0.002 mol), then NaBH(OAc)3 (0.54 g) (0.00255 mol.). The reaction mixture was stirred overnight at RT and then the insoluble material eliminated. After evaporating the solvent, the residue was purified by SiO2 chromatography (eluent: DCM/MeOH 98/2) to afford the titled compound and its stereoisomer. 7aS,6S stereoisomer (70 mg). NMR (CDCl3, 200 MHz): 7.45 (2H, d), 7.3 (1H, m), 7.2-7.1(4H, m), 4.25 (1H, dd), 4.05 (1H, d), 3.65 (2H, dd), 3.4(1H, m), 3.02 (1H, dd), 2.35-2.2 (1H, m), 2.0 (1H, bd).

Workup

  1. customwas prepared
  2. customAfter evaporating the solvent
  3. customthe residue was purified by SiO2 chromatography (eluent: DCM/MeOH 98/2)

Sources & evidence

ORD record
ord-d36fbc0a06ef48a49fc3e81ba82b11d6
Source dataset
uspto-grants-2004_03
Patent number
US06710064B2

Linked notes

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