Hydrochloric Acid → HCID 70944699, compound

HRID 2401240Notes

Reaction equation

HRID 2401240 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]2[CH2:26][CH2:25]2)[N:20]=[CH:19][N:18]=1.CCN(C(C)C)C(C)C.Cl.CCOCC>CN1CCCC1=O.C(OCC)(=O)C>[ClH:16].[CH:24]1([C:21]2[N:20]=[CH:19][N:18]=[C:17]([NH:12][CH2:11][C:9]3[CH:10]=[C:5]4[CH:4]=[C:3]([C:2]([F:1])([F:14])[F:15])[NH:13][C:6]4=[N:7][CH:8]=3)[C:22]=2[CH3:23])[CH2:26][CH2:25]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 65645365HCID 65645365, compound2×HCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×

Product 1

HCID 70944699HCID 70944699, compoundYield 5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

1-[2-(Trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methanamine (Intermediate 5, 185 mg, 0.516 mmol), 4-chloro-6-cyclopropyl-5-methylpyrimidine (Intermediate 52, 122 mg, 0.722 mmol) and DIPEA (0.180 ml, 1.032 mmol) were added together in N-methyl-2-pyrrolidone (NMP) (2 ml) and the resulting mixture was heated at 120° C. for 18 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 SP4 column chromatography eluting with a gradient of 0-100% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure. The residue, contaminated with NMP, was dissolved in methanol and passed down an SCX column (1 g) eluting with methanol, followed by 2M ammonia/methanol. Product containing fractions were combined and evaporated under reduced pressure. The resulting residue was dissolved in methanol (1 mL), treated with 1M hydrochloric acid in ether (0.05 ml, 0.050 mmol), the solvent removed under reduced pressure and the residue dried under high vacuum at 40° C. for 4 hours to give the title compound as a yellow solid, (10 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 SP4 column chromatography
  7. washeluting with a gradient of 0-100% ethyl acetate and iso-hexane
  8. additionProduct containing fractions
  9. customevaporated under reduced pressure
  10. dissolutionwas dissolved in methanol
  11. washeluting with methanol
  12. additionProduct containing fractions
  13. customevaporated under reduced pressure
  14. dissolutionThe resulting residue was dissolved in methanol (1 mL)
  15. customthe solvent removed under reduced pressure
  16. customthe residue dried under high vacuum at 40° C. for 4 hours

Sources & evidence

ORD record
ord-b85c1f62684e4af381e806b53ce4fc63
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

Loading…