Sodium Cyanide → 4-{4-[1-((R)-3-amino-1-methyl-propyl)-piperidin-4-ylamino]-phenoxy}-benzoic acid methyl ester

HRID 1726286Notes

Reaction equation

HRID 1726286 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1.O=[C:20]1[CH2:25][CH2:24][N:23]([C@H:26]([CH3:30])[CH2:27][C:28]#[N:29])[CH2:22][CH2:21]1.[C-]#N.[Na+]>O.CO>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][CH:20]3[CH2:25][CH2:24][N:23]([C@H:26]([CH3:30])[CH2:27][CH2:28][NH2:29])[CH2:22][CH2:21]3)=[CH:13][CH:12]=2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 8929Sodium CyanideHCID 21907042Methyl 4-(4-aminophenoxy)benzoateHCID 68972438(betaR)-beta-Methyl-4-oxo-1-piperidinepropanenitrile

Product 1

HCID 689723134-{4-[1-((R)-3-amino-1-methyl-propyl)-piperidin-4-ylamino]-phenoxy}-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Using general procedure A with 4-(4-amino-phenoxy)-benzoic acid methyl ester (see EXAMPLE 96) (300 mg, 1.2 mmol) and (R)-3-(4-oxo-piperidin-1-yl)-butyronitrile (225 mg, 1.4 mmol) followed by general procedure J gave a green oil, which was subsequently treated with a solution of NaCN (175 mg) in H2O (5 mL) and MeOH (5 mL). The mixture was stirred at room temperature for 20 minutes to afford 4-{4-[1-((R)-3-amino-1-methyl-propyl)-piperidin-4-ylamino]-phenoxy}-benzoic acid methyl ester as a white solid (238 mg, 48% over 2 steps) following work-up and purification.

Workup

  1. customgave a green oil, which

Sources & evidence

ORD record
ord-8509768dc27a4209a745b6de30ffac4f
Source dataset
uspto-grants-2009_02
Patent number
US07491735B2

Reaction notes

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