Diisopropylethylamine → 6-(1-Fluoroethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine

HRID 2401225Notes

Reaction equation

HRID 2401225 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[NH:13][C:6]2=[N:7][CH:8]=[C:9]([CH2:11][NH2:12])[CH:10]=[C:5]2[CH:4]=1.Cl[C:17]1[CH:22]=[C:21]([CH:23]([F:25])[CH3:24])[N:20]=[CH:19][N:18]=1.CCN(C(C)C)C(C)C>CN1CCCC1=O.C(OCC)(=O)C>[F:25][CH:23]([C:21]1[N:20]=[CH:19][N:18]=[C:17]([NH:12][CH2:11][C:9]2[CH:10]=[C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:14])[F:15])[NH:13][C:6]3=[N:7][CH:8]=2)[CH:22]=1)[CH3:24]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×HCID 838541004-Chloro-6-(1-fluoroethyl)pyrimidine2×

Product 1

HCID 513561286-(1-Fluoroethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamineYield 14.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-[2-(Trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methanamine (Intermediate 5, 112 mg, 0.521 mmol), 4-chloro-6-(1-fluoroethyl)pyrimidine (Intermediate 21, 125 mg, 0.781 mmol) and DIPEA (0.182 mL, 1.041 mmol) were added together in N-methyl-2-pyrrolidone (3 mL) and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was heated at 100° C. for 1 hour and allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was separated, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by MDAP. Product containing fractions were combined and evaporated under reduced pressure. The resulting solid was dried under high vacuum at 45° C. for 18 hours to give the title compound as a white solid (25 mg);

Workup

  1. temperatureThe reaction mixture was heated at 100° C. for 1 hour
  2. temperatureto cool to room temperature
  3. washwashed with water and brine
  4. customThe organic layer was separated
  5. customdried under magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by MDAP
  8. additionProduct containing fractions
  9. customevaporated under reduced pressure
  10. customThe resulting solid was dried under high vacuum at 45° C. for 18 hours

Sources & evidence

ORD record
ord-2546095be7324a8f9e5611f451996ebd
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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