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

HRID 914012ノート

反応式

HRID 914012 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 6342Acetonitrile溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-45c40d7abb2845a3a4f97ea00af436ed
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

反応ノート

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