Acetic Acid → HCID 25159784, compound

HRID 913991Notes

Reaction equation

HRID 913991 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:26]([F:29])([F:28])[F:27])=[CH:8][C:9]=2[CH2:11][O:12][CH2:13][C:14]2([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:4]=[N:3]1.[C:30]([BH3-])#N.[Na+].C=O.C(O)(=O)C>C(#N)C.C(O)(=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:26]([F:29])([F:28])[F:27])=[CH:8][C:9]=2[CH2:11][O:12][CH2:13][C:14]2([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:15][CH2:16][N:17]([CH3:30])[CH2:18][CH2:19]2)[CH:4]=[N:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 25159782HCID 25159782, compound

Product 1

HCID 25159784HCID 25159784, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-methyl-7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)-1H-indazole (65 mg, 0.161 mmol) and sodium cyanoborohydride (20 mg, 0.322 mmol) in acetonitrile (1 mL) at room temperature was added formalin (50 μL). To this was added 1 drop of acetic acid. After 5 min, a second drop of acetic acid was added and the reaction stirred at room temperature for 15 min. The reaction was concentrated and loaded onto a strong cation exchange cartridge in methanol. The cartridge was washed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated to give 19 mg (28%). 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.95 (s, 1H), 7.31 (s, 1H), 7.23 (m, 4H), 7.17 (m, 1H), 4.66 (s, 2H), 3.90 (s, 3H), 3.47 (s, 2H), 2.51 (m, 2H), 2.18 (s, 3H), 2.05-2.25 (m, 4H), 1.91 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 143.7, 139.5, 135.1, 133.8, 128.3, 127.2, 126.2, 124.74, 124.67 (q, J=272 Hz), 124.6, 122.6 (q, J=33 Hz), 121.3, 119.6 (q, J=3.8 Hz), 79.2, 70.6, 51.9, 46.2, 40.6, 38.2, 32.5. Mass spec.: 418.15 (MH)+. Accurate mass spec.: m/z 418.2119 [MH]+, Δ=3.1 ppm.

Workup

  1. concentrationThe reaction was concentrated
  2. washThe cartridge was washed with several volumes of methanol which
  3. washThe product was eluted with 2 M ammonia in methanol
  4. concentrationconcentrated
  5. customto give 19 mg (28%)

Sources & evidence

ORD record
ord-4c54e648b4764a6c9a938185fedaf728
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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