Water → HCID 66791398, compound

HRID 2091978Notes

Reaction equation

HRID 2091978 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-ba1b0562ffd048af9e547eb44bbf0a9a
Source dataset
uspto-grants-2013_05
Patent number
US08440682B2

Reaction notes

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