Sodium hydride → 6-[2-(2-Chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]isonicotinonitrile

HRID 626678Notes

Reaction equation

HRID 626678 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:9]=[C:8]([C:10]#[N:11])[CH:7]=[CH:6][N:5]=1.Cl[C:13]1[C:18]2=[CH:19][N:20]([C:22]3[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:29])[N:21]=[C:17]2[CH:16]=[CH:15][N:14]=1>CN(C=O)C>[Cl:29][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([F:28])[C:22]=1[N:20]1[CH:19]=[C:18]2[C:13]([NH:3][C:4]3[N:5]=[CH:6][CH:7]=[C:8]([CH:9]=3)[C:10]#[N:11])=[N:14][CH:15]=[CH:16][C:17]2=[N:21]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 70155242-AminoisonicotinonitrileHCID 866970434-Chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 696713726-[2-(2-Chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]isonicotinonitrileYield 10.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (12 mg, 0.30 mmol) was added to a solution of 2-amino-4-cyanopyridine (36 mg, 0.30 mmol) in DMF (2 mL) in a microwave vial and stirred for 5 minutes. 4-Chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine (76 mg, 0.27 mmol) was added and then the vial was sealed, purged with nitrogen and irradiated at 150° C. for 10 minutes in the microwave. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (10 mg, 10% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.61 (s, 1H), 8.77 (dd, J=5.2, 0.9 Hz, 1H), 7.99 (d, J=7.3 Hz, 1H), 7.85 (s, 1H), 7.81-7.80 (m, 2H), 7.73 (d, J=8.2 Hz, 1H), 7.67 (t, J=9.0 Hz, 1H), 7.58 (dd, J=7.3, 0.9 Hz, 1H). LCMS (Method B): RT=2.98 min, m/z: 365 [M+H+].

Workup

  1. customthe vial was sealed
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 10 minutes in the microwave
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-d1ed04d3124b43d088e7618fc1b2a1b2
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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