p-(Trifluoromethoxy)phenyl isocyanate → 1-((1R,2R)-2-((S)-1-(4-Cyanophenyl)piperidin-3-ylamino)cyclohexyl)-3-(4-(trifluoromethoxy)phenyl)urea
Reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23](=[O:35])CC3C4C(=CC=CC=4)N(C)C=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].[N:36]([C:39]1[CH:44]=[CH:43][C:42]([O:45][C:46]([F:49])([F:48])[F:47])=[CH:41][CH:40]=1)=C=O>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]([NH:36][C:39]3[CH:44]=[CH:43][C:42]([O:45][C:46]([F:47])([F:48])[F:49])=[CH:41][CH:40]=3)=[O:35])[CH2:10]2)=[CH:7][CH:8]=1)#[N:2]Participants
Procedure
1-((1R,2R)-2-((S)-1-(4-Cyanophenyl)piperidin-3-ylamino)cyclohexyl)-3-(4-(trifluoromethoxy)phenyl)urea was synthesized using 4-((S)-3-((1R,2R)-2-aminocyclohexylamino)piperidin-1-yl)benzonitrile (from intermediate D, Example 10) (40 mg, 0.13 mmol) and 1-isocyanato-4-(trifluoromethoxy)benzene (27.2 mg, 0.13 mmol) according to General Procedure G to give 25 mg (37.2%) of white solid. Anal. Calcd. for C26H30F3N5O2 m/z 501.2, found: 502.0 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.7 (s, 1H), 7.49 (d, J=9 Hz, 2H), 7.40 (d, J=8.9 Hz, 2H), 7.23 (d, J=8.9 Hz, 2H), 6.92 (d, J=8.9 Hz, 2H), 6.13 (d, J=7.4 Hz, 1H), 3.87 (d, J=11.8 Hz, 1H), 3.76 (d, J=12.9 Hz, 1H), 3.28 (m, 1H), 2.79 (m, 1H), 2.60 (m, 2H), 2.44 (m, 2H), 1.91 (m, 1H), 1.65 (m, 3H), 1.48 (m, 1H), 1.24 (m, 6H), 1.11 (m, 1H).
Sources & evidence
- ORD record
- ord-5693897afb944b55863b6b0574813c01
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08710049B2
Reaction notes
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