Water → HCID 66791398, compound

HRID 1966061Notes

Reaction equation

HRID 1966061 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:13]([CH2:14][CH3:15])[CH2:12][CH:11]([NH:16][C:17]2[N:22]=[CH:21][C:20]([OH:23])=[CH:19][N:18]=2)[CH2:10][CH:9]1[CH2:24][CH3:25])=[O:7])([CH3:4])([CH3:3])C.C(=O)([O-])[O-].[K+].[K+].[CH2:32](N)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.O>CN(C=O)C>[CH:1]([O:5][C:6]([N:8]1[CH:13]([CH2:14][CH3:15])[CH2:12][CH:11]([NH:16][C:17]2[N:18]=[CH:19][C:20]([O:23][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:21][N:22]=2)[CH2:10][CH:9]1[CH2:24][CH3:25])=[O:7])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 7504BenzylamineHCID 11430Potassium CarbonateHCID 66790529HCID 66790529, compound

Product 1

HCID 66791398HCID 66791398, compoundYield 171.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2,6-diethyl-4-(5-hydroxy-pyrimidin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (1.72 mmol, 580 mg) and potassium carbonate (3.23 mmol, 1.12 g) in DMF (12 mL) is added benzylamine (3.53 mmol, 0.42 mL) at room temperature and stirred for 2 hours. Water is added to the mixture, and the precipitate is collected and washed with hexane to give 4-(5-benzyloxy-pyrimidin-2-ylamino)-2,6-diethylpiperidine-1-carboxylic acid isopropyl ester (1.26 g, 74%) as a colorless solid. To a solution of 4-(5-benzyloxy-pyrimidin-2-ylamino)-2,6-diethylpiperidine-1-carboxylic acid isopropyl ester (2.86 mmol, 1.26 g) in DMF (28 mL) is added sodium hydride (60% oil suspension, 5.72 mmol, 230 mg) at 0° C. and stirred at room temperature for 20 min. To the mixture is added 1-bromomethyl-3,5-bis(trifluoromethyl)benzene (4.29 mmol, 0.79 mL) at 0° C. and stirred at room temperature for 17 hours. To the mixture is added sodium hydride (60% oil suspension, 2.86 mmol, 115 mg) and 1-bromomethyl-3,5-bis(trifluoromethyl)benzene (2.73 mmol, 0.5 mL) at 0° C. and stirred at room temperature for 5 hours. To the mixture is added water, and extracted with EtOAc. The combined organic layer is dried over Na2SO4, filtrated, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give cis-4-[(5-benzyloxy-pyrimidin-2-yl)-(3,5-bis(trifluoromethyl)benzyl)-amino]-2,6-diethylpiperidine-1-carboxylic acid 4-methoxycarbonyl-cyclohexyl ester (880 mg, 46%); ESI-MS m/z: 667 [M+1]+, Retention time 2.69 min (condition A).

Workup

  1. customthe precipitate is collected
  2. washwashed with hexane

Sources & evidence

ORD record
ord-c08810c4bf8c4358b10e1655d178aee5
Source dataset
uspto-grants-2013_04
Patent number
US08420641B2

Reaction notes

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