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

HRID 914012Notes

Reaction equation

HRID 914012 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-45c40d7abb2845a3a4f97ea00af436ed
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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