p-(Trifluoromethoxy)phenyl isocyanate → 1-Propan-2-yl-1-[3-(1,3-thiazol-2-yl)benzyl]-3-[4-(trifluoromethoxy)phenyl]urea

HRID 711292Notes

Reaction equation

[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:7]=[C:8]([CH:14]=[CH:15][CH:16]=1)[CH2:9][NH:10][CH:11]([CH3:13])[CH3:12].[N:17]([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1)=[C:18]=[O:19]>ClCCl>[CH3:12][CH:11]([N:10]([CH2:9][C:8]1[CH:14]=[CH:15][CH:16]=[C:6]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[CH:7]=1)[C:18]([NH:17][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:28])([F:29])[F:30])=[CH:22][CH:21]=1)=[O:19])[CH3:13]

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of N-[3-(1,3-thiazol-2-yl)benzyl]propan-2-amine (35 mg, 0.15 mmol, 1.0 eq) in dichloromethane (2.5 mL) was added 1-isocyanato-4-(trifluoromethoxy)benzene (30 mg, 0.15 mmol, 1.0 eq) and the reaction was stirred at 23° C. for 16 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by reverse phase liquid chromatography (Gemini-NX C18, 5 μm, 30×100 mm column; 0-100% CH3CN/H2O gradient w/0.10% TFA present) to yield 1-propan-2-yl-1-[3-(1,3-thiazol-2-yl)benzyl]-3-[4-(trifluoromethoxy)phenyl]urea as a white solid. 1H NMR (500 MHz, DMSO): δ 8.58 (s, 1 H); 7.93-7.88 (m, 2 H); 7.80-7.75 (m, 2 H); 7.56 (d, J=8.7 Hz, 2 H); 7.45 (t, J=7.7 Hz, 1 H); 7.38 (d, J=7.7 Hz, 1 H); 7.22 (d, J=8.6 Hz, 2 H); 4.63 (s, 2 H); 4.54-4.48 (m, 1 H); 1.12 (d, J=6.6 Hz, 6 H). LRMS m/z (M+H) 436.1 found, 436.1 required.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customthe resulting residue was purified by reverse phase liquid chromatography (Gemini-NX C18, 5 μm, 30×100 mm column; 0-100% CH3CN/H2O gradient w/0.10% TFA present)

Sources & evidence

ORD record: ord-08ee1f90abef4afc9a91e15218473544
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181261B2

Reaction notes

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