N-methyl-2-pyrrolidone → HCID 67388631, compound

HRID 269841Notes

Reaction equation

HRID 269841 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[C:5]([C:16]([NH2:18])=[O:17])=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:42]=[CH:41][C:23]([CH2:24][N:25]([CH2:33][CH2:34][N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)C(=O)OC(C)(C)C)=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C.CN1C(=O)CCC1>O>[ClH:1].[ClH:1].[ClH:1].[CH3:15][C:11]1[CH:10]=[C:9]([NH:8][C:6]2[C:5]([C:16]([NH2:18])=[O:17])=[CH:4][N:3]=[C:2]([NH:19][C:20]3[CH:42]=[CH:41][C:23]([CH2:24][NH:25][CH2:33][CH2:34][N:35]4[CH2:36][CH2:37][O:38][CH2:39][CH2:40]4)=[CH:22][CH:21]=3)[N:7]=2)[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 184608435-Pyrimidinecarboxamide, 2-chloro-4-[(3-methylphenyl)amino]-HCID 67387804Carbamic acid, [(4-aminophenyl)methyl][2-(4-morpholinyl)ethyl]-, 1,1-dimethylethyl ester

Product 1

HCID 67388631HCID 67388631, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 1.0 g of 2-chloro-4-(3-methylanilino)pyrimidine-5-carboxamide, 1.6 g of tert-butyl 4-aminobenzyl(2-morpholin-4-ylethyl)carbamate, 1.33 ml of diisopropylethylamine and 10 ml of NMP was stirred overnight at 130° C. The reaction mixture was cooled down to room temperature, and then mixed with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, the solvent was evaporated, and the resulting residue was purified by a silica gel column chromatography (chloroform:methanol). Then, a 750 mg portion of 780 mg of the resulting compound was stirred overnight at room temperature in a mixed solution of 75 ml methanol and 30 ml 6 M hydrochloric acid. The reaction mixture was concentrated, and then the resulting crystals were washed with methanol to obtain 510 mg of 4-[(3-methylphenyl)amino]-2-[(4-{[(2-morpholin-4-ylethyl)amino]methyl}phenyl)amino]pyrimidine-5-carboxamide trihydrochloride as colorless crystals.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. customthe solvent was evaporated
  5. customthe resulting residue was purified by a silica gel column chromatography (chloroform:methanol)
  6. stirringThen, a 750 mg portion of 780 mg of the resulting compound was stirred overnight at room temperature in a mixed solution of 75 ml methanol and 30 ml 6 M hydrochloric acid
  7. concentrationThe reaction mixture was concentrated
  8. washthe resulting crystals were washed with methanol

Sources & evidence

ORD record
ord-e3c2e8ec5c494b9198cc618e2ab8b3f1
Source dataset
uspto-grants-2008_11
Patent number
US07449456B2

Reaction notes

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