Hydrochloric Acid → HCID 70944636, compound

HRID 2401235Notes

Reaction equation

HRID 2401235 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:16][C:17]1[C:22]([CH3:23])=[C:21]([CH:24]([F:26])[CH3:25])[N:20]=[CH:19][N:18]=1.CCN(C(C)C)C(C)C.Cl.C(OCC)C>CN1CCCC1=O.C(OCC)(=O)C>[ClH:16].[F:26][CH: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

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×HCID 83854099HCID 83854099, compound2×

Product 1

HCID 70944636HCID 70944636, compoundYield 12.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

1-[2-(Trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methanamine (Intermediate 5, 100 mg, 0.465 mmol), 4-chloro-6-(1-fluoroethyl)-5-methylpyrimidine (Intermediate 45, 153 mg, 0.874 mmol) and DIPEA (0.162 mL, 0.929 mmol) were added together in N-methyl-2-pyrrolidone (NMP) (3 mL) and the resulting mixture was heated at 100° C. for 2 hours 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 column chromatography (Biotage SP4, 25+M) eluting with a gradient of 0-100% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure. The residue (26 mg) was dissolved in methanol (2 mL), treated with 1M HCl in diethyl ether (0.1 mL, 0.100 mmol) and the resulting mixture was evaporated under reduced pressure. The resulting solid was dried under high vacuum at 40° C. for 18 hours to give the title compound as a white solid (23 mg);

Workup

  1. temperatureto cool to room temperature
  2. washwashed with water and brine
  3. customThe organic layer was separated
  4. customdried under magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography (Biotage SP4, 25+M)
  7. washeluting with a gradient of 0-100% ethyl acetate and iso-hexane
  8. additionProduct containing fractions
  9. customevaporated under reduced pressure
  10. dissolutionThe residue (26 mg) was dissolved in methanol (2 mL)
  11. customthe resulting mixture was evaporated under reduced pressure
  12. customThe resulting solid was dried under high vacuum at 40° C. for 18 hours

Sources & evidence

ORD record
ord-db1eadcbca0c471497cba36cee2d0dfd
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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