Acetic Acid → HCID 25159786, compound

HRID 913994Notes

Reaction equation

HRID 913994 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][O:15][CH2:16][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)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:30]([BH3-])#N.[Na+].C=O.C(O)(=O)C>C(#N)C.C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][O:15][CH2:16][C:17]3[CH:18]=[C:19]([C:26]([F:27])([F:28])[F:29])[CH:20]=[C:21]4[C:25]=3[NH:24][N:23]=[CH:22]4)[CH2:13][CH2:12][N:11]([CH3:30])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57545927HCID 57545927, compound

Product 1

HCID 25159786HCID 25159786, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 7-(((4-(4-fluorophenyl)piperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)-1H-indazole (50 mg, 0.123 mmol) and sodium cyanoborohydride (7.7 mg, 0.123 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 28 mg (54%). 1H-NMR (CDCl3, 500 MHz) δ 9.81 (bs, 1H), 8.06 (s, 1H), 7.94 (s, 1H), 7.33 (m, 2H), 7.26 (s, 1H), 7.12 (m, 2H), 4.73 (s, 2H), 3.54 (s, 2H), 2.55 (m, 2H), 2.22 (m, 7H), 1.96 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 162.6, 160.6, 139.6, 135.4, 128.7, 128.6, 124.7 (q, J=272 Hz), 123.3 (q, J=32 Hz), 122.9, 121.8, 120.3 (q, J=2.9 Hz), 118.4 (q, J=4.8 Hz), 115.8, 115.6, 80.4, 71.9, 51.8, 46.3, 40.3, 32.9. Mass spec.: 422.13 (MH)+. Accurate mass spec.: m/z 422.1836 [MH]+, Δ=4.6 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 28 mg (54%)

Sources & evidence

ORD record
ord-fa4634e77ddd444ba8952671577ab10b
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…