Formaldehyde → (+/-)-5-Bromo-7-(1-((4-(4-fluorophenyl)-1-methylpiperidin-4-yl)methoxy)ethyl)-1H-indazole

HRID 914012노트

반응식

HRID 914012 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2.[C:28]([BH3-])#N.[Na+].C=O.O.C(OCC)C>C(#N)C.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH2:20][CH2:19][N:18]([CH3:28])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2

참가 물질

7

반응물 4

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 21584184Diethylether waterHCID 57546134(+/-)-5-Bromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole

생성물 1

HCID 25160191(+/-)-5-Bromo-7-(1-((4-(4-fluorophenyl)-1-methylpiperidin-4-yl)methoxy)ethyl)-1H-indazole

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 6342Acetonitrile용매

실험 절차

To a suspension (±)-5-bromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole (33 mg, 0.076 mmol) and sodium cyanoborohydride (9.6 mg, 0.15 mmol) in acetonitrile (1 mL) was added formalin (50 μl) and one drop of acetic acid. The reaction was stirred at room temperature for 1 h, poured into water/diethyl ether, washed with 1M sodium hydroxide, then water, and concentrated. The crude residue was loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated. 1H-NMR (CDCl3, 500 MHz) δ 9.78 (bs, 1H), 7.89 (s, 1H), 7.73 (d, J=1.5, 1H), 7.25 (m, 2H), 7.10 (d, J=1.2, 1H), 7.05 (m, 2H), 4.49 (q, J=6.7, 1H), 3.39 (d, J=9.2, 1H), 3.25 (d, J=9.2, 1H), 2.60 (m, 1H), 2.53 (m, 1H), 1.95-2.32 (m, 5H), 2.21 (s, 3H), 1.92 (m, 1H), 1.41 (d, J=6.7, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 162.5, 160.6, 135.9, 133.7, 128.7 (d, J=7.7), 128.0, 126.5, 125.5, 122.2, 115.6, 115.4, 113.5, 78.2, 51.9, 51.7, 46.2, 40.3, 32.8, 32.5, 22.2. Mass spec.: 445.93 (MH)+.

후처리

  1. washwashed with 1M sodium hydroxide
  2. concentrationwater, and concentrated
  3. customThe cartridge was flushed with several volumes of methanol which
  4. washThe product was eluted with 2M ammonia in methanol
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-45c40d7abb2845a3a4f97ea00af436ed
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

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