Dichloromethane → 1-(4-Amino-pyrimidin-2-ylmethyl)-piperidine-4-carboxylic acid tert-butylamide

HRID 1486701Notes

Reaction equation

HRID 1486701 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([NH2:9])[CH:6]=[CH:5][N:4]=1.[C:10]([NH:14][C:15]([CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].C(Cl)Cl.[OH-].[Na+]>CO.O>[C:10]([NH:14][C:15]([CH:17]1[CH2:22][CH2:21][N:20]([CH2:2][C:3]2[N:8]=[C:7]([NH2:9])[CH:6]=[CH:5][N:4]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 7175833N-tert-butylpiperidine-4-carboxamideHCID 212988272-(Chloromethyl)pyrimidin-4-amine

Product 1

HCID 867065331-(4-Amino-pyrimidin-2-ylmethyl)-piperidine-4-carboxylic acid tert-butylamideYield 94%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of 2-chloromethyl-pyrimidin-4-ylamine (Imperial Chemical Industries PLC Patent: U.S. Pat. No. 4,447,441 A1, 1984; 300 mg, 2.1 mmol) in methanol (25 mL) is treated with piperidine-4-carboxylic acid tert-butylamide (404 mg, 2.19 mmol) and TEA (0.872 mL, 6.27 mmol). The resulting mixture is heated at reflux overnight. DCM (25 mL) and water (25 mL) are added followed by NaOH 1M to adjust at pH 10. The organic phase is separated. The aqueous phase is extracted with DCM (25 mL). The combined organic phases are dried over MgSO4, filtered and evaporated. Evaporation of the solvent yields the crude product (0.57 g, 94%) as a brownish solid; LC-MS A: tR=0.40 min; [M+H]+=292.14.

Workup

  1. temperatureThe resulting mixture is heated
  2. temperatureat reflux overnight
  3. customThe organic phase is separated
  4. extractionThe aqueous phase is extracted with DCM (25 mL)
  5. dry with materialThe combined organic phases are dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customEvaporation of the solvent

Sources & evidence

ORD record
ord-db09b09acbf6436cb68efe04beeb0e7b
Source dataset
uspto-grants-2016_08
Patent number
US09428456B2

Reaction notes

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