N-methyl-2-pyrrolidone → HCID 51356421, compound

HRID 2401234Notes

Reaction equation

HRID 2401234 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[C:22]([CH3:23])=[C:21]([CH2:24][CH3:25])[N:20]=[CH:19][N:18]=1.CCN(C(C)C)C(C)C.CN1CCCC1=O>C(OCC)(=O)C>[CH2:24]([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)[C:22]=1[CH3:23])[CH3:25]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 63549460HCID 63549460, compound2×HCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×

Product 1

HCID 51356421HCID 51356421, compoundYield 29.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

1-[2-(Trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methanamine (Intermediate 5, 129 mg, 0.6 mmol), 4-chloro-6-ethyl-5-methylpyrimidine (Intermediate 41, 141 mg, 0.900 mmol) and DIPEA (0.210 mL, 1.200 mmol) were added together with N-methyl-2-pyrrolidone (1 mL) and the resulting mixture was stirred and heated to 120° C. for 6 hours. The reaction mixture was diluted with ethyl acetate and washed with sodium hydrogen carbonate solution, 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 triturated with ether/isohexane (1:1) and the resulting solid was collected and dried affording the title compound (60 mg);

Workup

  1. washwashed with sodium hydrogen carbonate solution, water and brine
  2. customThe organic layer was separated
  3. customdried under magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by MDAP
  6. additionProduct containing fractions
  7. customevaporated under reduced pressure
  8. customThe resulting solid was triturated with ether/isohexane (1:1)
  9. customthe resulting solid was collected
  10. customdried

Sources & evidence

ORD record
ord-596f2b6cdd1945eea3d68ee95865a025
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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