Acetic Acid → HCID 57546102, compound

HRID 913999Notes

Reaction equation

HRID 913999 reaction equation
[C:1]1([C:7]2([CH2:13][O:14][CH:15]([C:17]3[CH:18]=[C:19]([C:26]([F:29])([F:28])[F:27])[CH:20]=[C:21]4[C:25]=3[NH:24][N:23]=[CH:22]4)[CH3:16])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:30]([BH3-])#N.[Na+].C=O.C(O)(=O)C>C(#N)C.C(O)(=O)C>[CH3:30][N:10]1[CH2:11][CH2:12][C:7]([CH2:13][O:14][CH:15]([C:17]2[CH:18]=[C:19]([C:26]([F:28])([F:27])[F:29])[CH:20]=[C:21]3[C:25]=2[NH:24][N:23]=[CH:22]3)[CH3:16])([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 25159918HCID 25159918, compound

Product 1

HCID 57546102HCID 57546102, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of (±)-7-(1-((4-phenylpiperidin-4-yl)methoxy)ethyl)-5-(trifluoromethyl)-1H-indazole (35 mg, 0.087 mmol) and sodium cyanoborohydride (5.5 mg, 0.087 mmol) in acetonitrile (1 mL) at room temperature was added formalin (25 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 21 mg (58%). 1H-NMR (CDCl3, 500 MHz) δ 9.78 (bs, 1H), 8.02 (s, 1H), 7.90 (s, 1H), 7.28-7.49 (m, 5H), 7.21 (s, 1H), 4.62 (q, J=6.7 Hz, 1H), 3.48 (s, 3H), 3.45-3.51 (m, 3H), 3.31 (d, J=8.9 Hz, 1H), 2.62 (m, 2H), 2.39 (m, 1H), 2.12-2.31 (m, 7H), 2.06 (m, 1H), 1.95 (m, 1H), 1.44 (d, J=6.7 Hz, 3H); 13C-NMR (CDCl3, 126 MHz) δ 138.1, 135.2, 128.9, 127.5, 127.1, 126.9, 124.7 (q, J=272 Hz), 123.3, 119.8 (q, J=2.9 Hz), 118.1 (q, J=3.8 Hz), 79.0 (br), 78.4, 52.0, 51.8, 50.8, 46.1, 40.7, 32.5, 32.3, 22.2. Mass spec.: 418.18 (MH)+. Accurate mass spec.: m/z 418.2101 [MH]+, Δ=1.2 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 21 mg (58%)

Sources & evidence

ORD record
ord-9a53ddbcdb4e455d8f2e23e69980b41f
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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