Methanol → HCID 58920908, compound

HRID 1365514Notes

Reaction equation

HRID 1365514 reaction equation
[CH:1]1([NH:6][C:7]([NH:9][C:10]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([F:36])[CH:27]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24]C)[N:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Si](I)(C)(C)C.CO>C(Cl)(Cl)Cl>[CH:1]1([NH:6][C:7]([NH:9][C:10]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[C:28]([F:36])[CH:27]=2)([C:18]2[NH:19][C:20](=[O:24])[CH:21]=[CH:22][CH:23]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 887MethanolHCID 85247Trimethylsilyl iodide2×HCID 58920647HCID 58920647, compound

Product 1

HCID 58920908HCID 58920908, compoundYield 54.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

1-Cyclopentyl-3-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(6-methoxypyridin-2-yl)-2-phenylethyl)urea (25 mg, 0.049 mmol) was stirred in CHCl3 (1 mL) in a pyrex tube at room temperature. TMSI (0.04 mL) was added and the reaction mixture was refluxed for 3 h. Additional TMSI (0.04 mL) was added. The mixture was refluxed for an additional two hours. The mixture was cooled to room temperature and MeOH (1 mL) was added. The reaction mixture was concentrated. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc, came out 100% EtOAc) to give 1-cyclopentyl-3-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(6-oxo-1,6-dihydropyridin-2-yl)-2-phenylethyl)urea (13 mg, yield: 54%) as a white solid. LC-MS ESI (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=3.75 min, 488.12 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 12.06 (s, br, 1H), 7.52 (dd, J=8.8, 7.3 Hz, 1 H), 7.19 (t, J=7.0 Hz, 2 H), 7.12 (t, J=7.3 Hz, 2 H), 6.94 (s, br, 1 H), 6.83 (d, J=10 Hz, 1 H), 6.68 (d, J=7.3 Hz, 2 H), 6.61 (d, J=7.1 Hz, 1 H), 6.30 (d, J=8.8 Hz, 1 H), 6.15 (s, br, 1 H), 5.22 (s, br, 1 H), 4.32 (d, J=12.2 Hz, 1 H), 3.88-3.98 (m, 1 H), 3.19 (d, J=12.7 Hz, 1 H), 1.92-1.86 (m, 1 H), 1.83-1.74 (m, 1 H) 1.65-1.48 (m, 4 H), 1.43-1.35 (m, 1 H) 1.25-1.18 (m, 1 H).

Workup

  1. temperaturethe reaction mixture was refluxed for 3 h
  2. temperatureThe mixture was refluxed for an additional two hours
  3. concentrationThe reaction mixture was concentrated
  4. customThe residue was purified by flash chromatography (silica gel, hexanes/EtOAc

Sources & evidence

ORD record
ord-1d63eeb4dc16488085bb0e794505d257
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

Loading…