Acetic Acid → HCID 25159785, compound

HRID 913992Notes

Reaction equation

HRID 913992 reaction equation
[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([C:5]([CH2:15][O:16][CH2:17][C:18]3([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[CH:6][C:7]([C:11]([F:14])([F:13])[F:12])=[CH:8]2)=[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[CH:10]=[C:9]2[C:4]([C:5]([CH2:15][O:16][CH2:17][C:18]3([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:19][CH2:20][N:21]([CH3:30])[CH2:22][CH2:23]3)=[CH:6][C:7]([C:11]([F:13])([F:12])[F:14])=[CH:8]2)=[N:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 25159783HCID 25159783, compound

Product 1

HCID 25159785HCID 25159785, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-methyl-7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)-2H-indazole (58 mg, 0.144 mmol) and sodium cyanoborohydride (18 mg, 0.288 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 15 mg (25%). 1H-NMR (CDCl3, 500 MHz) δ 7.97 (s, 1H), 7.85 (s, 1H), 7.41 (m, 2H), 7.34 (m, 2H), 7.22 (m, 1H), 4.82 (s, 2H), 4.21 (s, 3H), 3.58 (s, 2H), 2.60 (m, 2H), 2.20-2.33 (m, 4H), 2.22 (s, 3H), 2.06 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 147.6, 135.1, 129.3, 128.3, 127.4, 126.1, 125.5, 124.9 (q, J=272 Hz), 124.2 (q, J=32 Hz), 120.7, 118.7, 117.5 (q, J=4.8 Hz), 79.9, 68.7, 52.1, 46.2, 40.9, 40.7, 32.4. Mass spec.: 418.15 (MH)+. Accurate mass spec.: m/z 418.2019 [MH]+, Δ=0.7 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 15 mg (25%)

Sources & evidence

ORD record
ord-6c88ab483dfa48e2b237381f9b6999df
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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