Trifluoroacetic acid methylene chloride → 5-Cyclopropyl-7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-1H-indazole

HRID 914011Notes

Reaction equation

HRID 914011 reaction equation
[CH:1]1([C:4]2[CH:12]=[C:11]([CH2:13][O:14][CH2:15][C:16]3([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[C:10]3[C:6](=[CH:7][N:8](COCC[Si](C)(C)C)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C(Cl)Cl>>[CH:1]1([C:4]2[CH:5]=[C:6]3[C:10](=[C:11]([CH2:13][O:14][CH2:15][C:16]4([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)[CH:12]=2)[NH:9][N:8]=[CH:7]3)[CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57546153tert-Butyl 4-(((5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 251601925-Cyclopropyl-7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-1H-indazole

Procedure

tert-Butyl 4-(((5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (34 mg, 0.06 mmol) was treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 4 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvent was evaporated and the product purified by reverse phase HPLC to afford 10 mg (48%) as a clear oil. 1H-NMR (CD3OD, 500 MHz) δ 7.96 (s, 1H), 7.42-7.47 (m, 5H), 7.31-7.34 (m, 1H), 7.01 (m, 1H), 4.71 (s, 2H), 3.51 (s, 2H), 3.24-3.28 (m, 2H), 2.89-2.95 (m, 2H), 2.46-2.49 (m, 2H), 2.16-2.21 (m, 2H), 1.98-2.02 (m, 2H); 13C-NMR (126 MHz, CD3OD) δ ppm 141.1, 138.1, 136.8, 133.5, 129.1, 127.2, 127.0, 125.6, 124.1, 120.1, 116.5, 78.9, 70.4, 41.1, 41.0, 28.9, 15.1, 8.1. Mass spec.: 362.22 (MH)+. Accurate mass spec.: m/z 362.2217 [MH]+, Δ=4.2 ppm.

Workup

  1. customThe solvent was removed in vacuo
  2. washAfter washing the column with several volumes of methanol
  3. washthe product was eluted
  4. washby washing the column with 2 M ammonia in methanol
  5. customThe solvent was evaporated
  6. customthe product purified by reverse phase HPLC
  7. customto afford 10 mg (48%) as a clear oil

Sources & evidence

ORD record
ord-117d79f758374fc6976ed10a699e6fe3
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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