Hydrochloric Acid → HCID 86673375, compound

HRID 2401236Notes

Reaction equation

HRID 2401236 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]([C:24]([F:27])([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][C: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])([F:27])[CH3:25]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×HCID 86673376HCID 86673376, compound2×

Product 1

HCID 86673375HCID 86673375, compoundYield 28%

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, 100 mg, 0.465 mmol), 4-chloro-6-(1,1-difluoroethyl)-5-methylpyrimidine (Intermediate 46, 134 mg, 0.697 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 stirred at room temperature for 2 hours. The reaction mixture was heated at 100° C. for 1 hour, allowed to cool to room temperature, 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, collect all) eluting with a gradient of 0-100% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure. The residue was triturated with DCM and the solid collected by filtration (53 mg), dissolved in methanol (2 mL), treated with 1M HCl in diethyl ether (0.16 mL, 0.160 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 (53 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 column chromatography (Biotage SP4, 25+M
  8. customcollect all)
  9. washeluting with a gradient of 0-100% ethyl acetate and iso-hexane
  10. additionProduct containing fractions
  11. customevaporated under reduced pressure
  12. customThe residue was triturated with DCM
  13. filtrationthe solid collected by filtration (53 mg)
  14. dissolutiondissolved in methanol (2 mL)
  15. customthe resulting mixture was evaporated under reduced pressure
  16. customThe resulting solid was dried under high vacuum at 40° C. for 18 hours

Sources & evidence

ORD record
ord-46b73363b3ad4e6fb93a1b71b7c1aabb
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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