Methyl iodide → HCID 67388766, compound

HRID 905687Notes

Reaction equation

HRID 905687 reaction equation
[CH3:1]N1CCCC1=O.[NH:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]3[N:27]=[C:26]([NH:28][CH2:29][C:30]4[C:35]([F:36])=[CH:34][CH:33]=[C:32]([F:37])[C:31]=4[F:38])[C:25]([C:39]([NH2:41])=[O:40])=[CH:24][N:23]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1.CI.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:1][N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:22]3[N:27]=[C:26]([NH:28][CH2:29][C:30]4[C:35]([F:36])=[CH:34][CH:33]=[C:32]([F:37])[C:31]=4[F:38])[C:25]([C:39]([NH2:41])=[O:40])=[CH:24][N:23]=3)=[CH:19][CH:20]=2)[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 67387810HCID 67387810, compound

Product 1

HCID 67388766HCID 67388766, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 10 ml portion of 1-methyl-2-pyrrolidone solution containing 800 mg of 2-{[4-(piperidin-4-yloxy)phenyl]amino}-4-[(2,3,6-trifluorobenzyl)amino]-pyrimidine-5-carboxamide was mixed with 0.12 ml of methyl iodide and 300 mg of potassium carbonate, followed by stirring at room temperature for 1 hour and then at 60° C. for 30 minutes. A 0.1 ml portion of methyl iodide was further added thereto, followed by stirring for 30 minutes. The reaction mixture was cooled down to room temperature, mixed with water and then extracted with an ethyl acetate-THF mixed solvent. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by a silica gel column chromatography (chloroform-methanol-aqueous ammonia) and further recrystallized from ethanol to obtain 197 mg of 2-({4-[(1-methylpiperidin-4-yl)oxy]phenyl}amino)-4-[(2,3,6-trifluorobenzyl)amino]pyrimidine-5-carboxamide as colorless crystals.

Workup

  1. waitat 60° C. for 30 minutes
  2. stirringby stirring for 30 minutes
  3. temperatureThe reaction mixture was cooled down to room temperature
  4. extractionextracted with an ethyl acetate-THF mixed solvent
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated
  8. customthe resulting residue was purified by a silica gel column chromatography (chloroform-methanol-aqueous ammonia)
  9. customfurther recrystallized from ethanol

Sources & evidence

ORD record
ord-7bc62edc38e348f191cfad02dc730666
Source dataset
uspto-grants-2011_09
Patent number
US08012959B2

Reaction notes

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