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

HRID 626678노트

반응식

HRID 626678 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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+].

후처리

  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)

출처 및 근거

ORD 기록
ord-d1ed04d3124b43d088e7618fc1b2a1b2
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309240B2

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