Acetic Acid → HCID 25159655, compound

HRID 913988Notes

Reaction equation

HRID 913988 reaction equation
[C:1]1([C:7]2([CH2:13][O:14][CH2:15][C:16]3[CH:17]=[C:18]([C:25]([F:28])([F:27])[F:26])[CH:19]=[C:20]4[C:24]=3[NH:23][N:22]=[CH:21]4)[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:29]([BH3-])#N.[Na+].C=O.C(O)(=O)C>C(#N)C.C(O)(=O)C>[CH3:29][N:10]1[CH2:11][CH2:12][C:7]([CH2:13][O:14][CH2:15][C:16]2[CH:17]=[C:18]([C:25]([F:27])([F:26])[F:28])[CH:19]=[C:20]3[C:24]=2[NH:23][N:22]=[CH:21]3)([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 25159651HCID 25159651, compound

Product 1

HCID 25159655HCID 25159655, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)-1H-indazole (62 mg, 0.159 mmol) and sodium cyanoborohydride (10 mg, 0.159 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. The product was purified by preparative HPLC. The trifluoroacetic acid salt was 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 37 mg (58%). 1H-NMR (CDCl3, 500 MHz) δ 9.60 (bs, 1H), 8.02 (s, 1H), 7.91 (s, 1H), 7.49 (m, 2H), 7.41 (m, 3H), 7.25 (s, 1H), 4.71 (s, 2H), 3.61 (s, 2H), 2.57 (m, 2H), 2.10-2.40 (m, 4H), 2.22 (s, 3H), 1.96 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 143.9, 139.5, 135.2, 129.0, 127.1, 126.9, 124.7 (q, J=272 Hz), 123.2 (q, J=32 Hz), 121.9, 120.1, 118.3, 80.8, 72.0, 52.0, 46.3, 40.7, 32.9. Mass spec.: 404.01 (MH)+. Accurate mass spec.: m/z [MH]+, Δ=4.4 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. customThe product was purified by preparative HPLC
  6. washThe cartridge was washed with several volumes of methanol which
  7. washThe product was eluted with 2 M ammonia in methanol
  8. concentrationconcentrated
  9. customto give 37 mg (58%)

Sources & evidence

ORD record
ord-ad8ea45455db44989f1ce11f78d505e5
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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