Trifluoroacetic acid methylene chloride → HCID 178506216, compound

HRID 914002Notes

Reaction equation

HRID 914002 reaction equation
[Br:1][C:2]1[N:3](COCC[Si](C)(C)C)[N:4]=[C:5]2[C:10]=1[CH:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:7]=[C:6]2[CH2:15][O:16][CH2:17][C:18]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]1.FC(F)(F)C(O)=O.C(Cl)Cl>>[Br:1][C:2]1[C:10]2[C:5](=[C:6]([CH2:15][O:16][CH2:17][C:18]3([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]3)[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[NH:4][N:3]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57546071HCID 57546071, compound

Product 1

HCID 178506216HCID 178506216, compound

Procedure

tert-Butyl 4-(((3-bromo-5-(trifluoromethyl)-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 compound purified by reverse phase HPLC to afford 5 mg (27%) as a clear oil. 1H-NMR (CD3OD, 500 MHz) δ 7.87 (s, 1H), 7.53 (s, 1H), 7.37-7.43 (m, 4H), 7.29-7.30 (m, 1H), 4.77 (s, 2H), 3.56 (s, 2H), 3.27-3.31 (m, 2H), 2.90-2.95 (m, 2H), 2.50-2.53 (m, 2H), 2.14-2.20 (m, 2H). Mass spec.: 468.08 (MH)+. Accurate mass spec.: m/z 468.1322 [MH]+, Δ=0.5 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 compound purified by reverse phase HPLC
  7. customto afford 5 mg (27%) as a clear oil

Sources & evidence

ORD record
ord-6c79d5bf5f4b473eb78bd32583ad6cc9
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…