5-fluoro-2-[(E)-1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-1H-pyrrolo[2,3-b]pyridine → 5-fluoro-2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 1515898노트

반응식

HRID 1515898 반응식
[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9](/[C:11](/[C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:12]/[CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[NH:8][C:5]2=[N:6][CH:7]=1>[Pd].CO>[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([CH:11]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH2:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[NH:8][C:5]2=[N:6][CH:7]=1

참가 물질

4

반응물 1

HCID 532303595-fluoro-2-[(E)-1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 532499855-fluoro-2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridine수율 60%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

반응 조건

온도
45 °C

실험 절차

A mixture of 5-fluoro-2-[(E)-1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 122, 300 mg, 0.75 mmol) and 10% palladium on activated carbon (0.2 g) in methanol (50 mL) was heated at 45° C. under hydrogen (50 psi) for 5 h. After cooling to room temperature, the catalyst was removed by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo. The residue was purified using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) to afford 5-fluoro-2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridine as a white solid (180 mg, 60%): LC/MS m/e calcd for C21H23FN2O3S [M+H]+ 403.49, observed 403.2; 1H NMR (400 MHz, CD3OD) δ ppm 8.01 (t, J=2.1 Hz, 1H), 7.91 (d, J=8.3 Hz, 2H), 7.60-7.67 (m, 3H), 6.41 (s, 1H), 4.44 (t, J=8.1 Hz, 1H), 3.90 (d, J=11.4 Hz, 2H), 3.25-3.30 (m, 2H), 3.08-3.14 (m, 3H), 2.24 (dt, J=14.1, 7.3 Hz, 1H), 1.99-2.07 (m, 1H), 1.72 (t, J=14.1 Hz, 2H), 1.32-1.52 (m, 3H).

후처리

  1. temperatureAfter cooling to room temperature
  2. customthe catalyst was removed by filtration
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified

출처 및 근거

ORD 기록
ord-0a86c7ec4d4b4971ab0a21adf4ee963c
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08222416B2

반응 노트

불러오는 중…