Formaldehyde → HCID 25160189, compound

HRID 914005Notes

Reaction equation

HRID 914005 reaction equation
[Cl: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][CH:24]=[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=O.[C:29]([BH3-])#N.[Na+]>C(#N)C.C(O)(=O)C>[Cl: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:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:16][CH2:17][N:18]([CH3:29])[CH2:19][CH2:20]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 25160187HCID 25160187, compound

Product 1

HCID 25160189HCID 25160189, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

(±)-5-Chloro-7-(1-((4-phenylpiperidin-4-yl)methoxy)ethyl)-1H-indazole (40 mg, 0.11 mmol) and formaldehyde (37 wt. % solution in water, 156 μL) were combined in acetonitrile (2 mL) and cooled to 0° C. The reaction was treated with sodium cyanoborohydride (34 mg, 0.54 mmol) and a few drops of acetic acid. The reaction was stirred at 0° C. for 30 min and at room temperature for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvents were evaporated to afford 30 mg (72%). 1H-NMR (CDCl3, 500 MHz) δ 7.89 (s, 1H), 7.55 (d, J=1.8 Hz, 1H), 7.39-7.42 (m, 2H), 7.34-7.37 (m, 1H), 7.27 (m, 2H), 6.97 (d, J=1.5 Hz, 1H), 4.52 (q, J=6.7 Hz, 1H), 3.35 (d, J=9.2 Hz, 1H), 3.23 (d, J=8.9 Hz, 1H), 3.11-3.26 (m, 2H), 2.45-2.53 (m, 2H), 2.49 (s, 3H), 2.38-2.40 (m, 2H), 2.25-2.30 (m, 2H), 1.46 (d, J=6.7 Hz, 3H); 13C-NMR (126 MHz, CDCl3) δ ppm 135.5, 133.6, 129.3, 127.5, 127.4, 126.9, 126.0, 124.9, 124.4, 119.1, 78.2, 51.5, 51.4, 44.4, 40.5, 30.2, 22.0. Mass spec.: 384.16 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. washAfter washing the column with several volumes of methanol
  3. washthe product was eluted
  4. washby washing the column with 2 M ammonia in methanol
  5. customThe solvents were evaporated
  6. customto afford 30 mg (72%)

Sources & evidence

ORD record
ord-e52930b9398747a0948a2e105ee7f327
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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