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

HRID 2401222Notes

Reaction equation

HRID 2401222 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[CH:22]=[C:21]([CH2:23][CH3:24])[N:20]=[CH:19][N:18]=1.CCN(C(C)C)C(C)C>CN1CCCC1=O.C(OCC)(=O)C>[CH2:23]([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)[CH:22]=1)[CH3:24]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 111372714-Chloro-6-ethylpyrimidine2×HCID 671114591H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-2×

Product 1

HCID 513558726-Ethyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamineYield 18.7%

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, 75 mg, 0.349 mmol), 4-chloro-6-ethylpyrimidine (Intermediate 12, 49.7 mg, 0.349 mmol) and DIPEA (0.122 mL, 0.697 mmol) in N-methyl-2-pyrrolidone (1 mL) were stirred in a microwave reactor at 120° C. for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (10 mL), brine (10 mL), water (10 mL) and brine (10 mL). The organic layer was dried (sodium sulfate), filtered and concentrated under reduced pressure. This solid was dissolved in a mixture of acetonitrile and DMSO (1:1) (0.9 mL) and purified by MDAP (2 injections). Fractions containing pure product were combined and concentrated under reduced pressure to give the title compound as a yellow oil (21 mg);

Workup

  1. washwashed with water (10 mL), brine (10 mL), water (10 mL) and brine (10 mL)
  2. dry with materialThe organic layer was dried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThis solid was dissolved in a mixture of acetonitrile and DMSO (1:1) (0.9 mL)
  6. custompurified by MDAP (2 injections)
  7. additionFractions containing pure product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d87fa7606ad94386b2da8dff699c32f6
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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