2-Aminothiazole → (R)-1-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(thiazol-2-yl)urea

HRID 1874155Notes

Reaction equation

HRID 1874155 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31](=O)[O:32]C(C)=C)([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.[NH2:37][C:38]1[S:39][CH:40]=[CH:41][N:42]=1.CN1CCCC1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31]([NH:37][C:38]2[S:39][CH:40]=[CH:41][N:42]=2)=[O:32])([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:5]=[C:6]([O:8][C:9]([F:13])([F:14])[CH:10]([F:12])[F:11])[CH:7]=1

Participants

5

Reactant 3

HCID 21552-AminothiazoleHCID 84541-MethylpyrrolidineHCID 59458545(R)-prop-1-en-2-yl 1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylcarbamate

Product 1

HCID 23582281(R)-1-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(thiazol-2-yl)ureaYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

(R)-prop-1-en-2-yl 1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylcarbamate (15 mg, 0.029 mmol) and 2-aminothiazole (8.2 mg, 0.082 mmol, 2.8 eq), and N-methylpyrrolidine (0.9 μl, 0.3 eq) were stirred in THF (0.3 mL) in a microwave vial. The reaction mixture was heated at 150° C. for 20 min under microwave irradiation. After cooling, the solvent was evaporated. The residue was purified by reverse phase HPLC (20-90% CH3CN in H2O with 0.1% TFA) to give pure (R)-1-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(thiazol-2-yl)urea as white solids (6.5 mg, yield: 40.6%). 1H NMR (400 MHz, CDCl3-D) δ ppm 7.29 (m, 1H), 7.23-7.18 (m, 3H), 7.16 (t, J=8.0 Hz, 2H), 7.02 (t, J=8.5 Hz, 2H), 6.94-6.89 (m, 4H), 6.71 (d, J=6.82 Hz, 2H), 5.86 (tt, J=47.1, 2.9 Hz, 1H), 3.84-3.75 (m, 2H); LC-MS (ESI) 552.28 (M+H), retention time=4.12 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run).

Workup

  1. temperatureAfter cooling
  2. customthe solvent was evaporated
  3. customThe residue was purified by reverse phase HPLC (20-90% CH3CN in H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-7900d065a4c84e918c50d480dff9ca21
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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