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

HRID 2401239Notes

Reaction equation

HRID 2401239 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]([CH2:24][F:25])[N:20]=[CH:19][N:18]=1.C(N(CC)CC)C.Cl.C(OCC)C>CN(C)C=O.CO.O>[ClH:16].[F:25][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]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×HCID 866733784-Chloro-6-(fluoromethyl)-5-methylpyrimidine2×

Product 1

HCID 709446486-(fluoromethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine hydrochlorideYield 2.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 1-[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methanamine (Intermediate 5, 300 mg, 1.394 mmol) in dry N,N-dimethylformamide (DMF) (15.000 mL) was treated with 4-chloro-6-(fluoromethyl)-5-methylpyrimidine (Intermediate 51, 336 mg, 2.091 mmol) and triethylamine (0.389 mL, 2.79 mmol). The reaction mixture was heated at 100° C. and stirred for 28 hours. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (2×20 mL). The organic extract was then dried under magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified on SP4 column chromatography (25+M) eluting with 0-100% isohexane-ethyl acetate. Product containing fractions were combined and evaporated under reduced pressure. The white residue was then dissolved in 1:1 ethyl acetate:methanol (2 mL) and 1M HCl in diethylether (0.05 mL, 0.543 mmol) was added. The mixture was then evaporated to dryness to give the title compound as a white solid (15 mg);

Workup

  1. extractionextracted with ethyl acetate (2×20 mL)
  2. extractionThe organic extract
  3. customwas then dried under magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe residue was purified on SP4 column chromatography (25+M)
  7. washeluting with 0-100% isohexane-ethyl acetate
  8. additionProduct containing fractions
  9. customevaporated under reduced pressure
  10. dissolutionThe white residue was then dissolved in 1:1 ethyl acetate
  11. customThe mixture was then evaporated to dryness

Sources & evidence

ORD record
ord-100209384bfe4b95bc6e03abe3afea36
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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