Triethylamine → HCID 178434310, compound

HRID 913837Notes

Reaction equation

HRID 913837 reaction equation
[CH3:1][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[CH:15]([O:17][CH2:18][C:19]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)[CH3:16].FC(F)(F)C(O)=O.C(Cl)Cl.C(=O)(OC(C)(C)C)OC(C)(C)C.C(N(CC)CC)C>ClCCl.N.CO>[CH3:1][C:2]1[C:10]2[C:5](=[C:6]([CH:15]([O:17][CH2:18][C:19]3([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])[CH2:21][CH2:20]3)[CH3:16])[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[NH:4][N:3]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) esterHCID 21863450Trifluoroacetic acid methylene chlorideHCID 57545963HCID 57545963, compound

Product 1

HCID 178434310HCID 178434310, compound

Reagents, catalysts & solvents 3

HCID 222AmmoniaCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(±)-tert-Butyl 4-((1-(3-methyl-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (94 mg, 0.15 mmol) was treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 1 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 concentrated to afford a crude product which was dissolved in dichloromethane (3 mL), cooled to 0° C., and treated with di-tert-butyl carbonate (63 mg, 0.29 mmol) and triethylamine (30 μL, 0.22 mmol). After 1 h, the reaction was treated with a few drops of 2 M ammonia in methanol and concentrated. The residue was dissolved in ethyl acetate, washed with water (2×), brine (2×), dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel (15% ethyl acetate/hexanes) afforded 62 mg (83%). 1H-NMR (CDCl3, 500 MHz) δ 7.81 (s, 1H), 7.38-7.41 (m, 2H), 7.30-7.35 (m, 3H), 7.19 (m, 1H), 4.56 (q, J=6.4 Hz, 1H), 3.76 (m, 2H), 3.40 (d, J=9.2 Hz, 1H), 3.29 (d, J=8.9 Hz, 1H), 2.99-3.06 (m, 2H), 2.54 (s, 3H), 2.11-2.31 (m, 2H), 1.75-1.87 (m, 2H), 1.42 (s, 9H), 1.40 (m, 3H). Mass spec.: 518.28 (MH)+.

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. concentrationThe solvent was concentrated
  6. customto afford a crude product which
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. washwashed with water (2×), brine (2×)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customFlash chromatography on silica gel (15% ethyl acetate/hexanes) afforded 62 mg (83%)

Sources & evidence

ORD record
ord-ff7546efc2bc483eb6385ff51441666d
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…