Phenyl isocyanate → HCID 71255514, compound
Reaction equation
Cl[C:2]1[C:11]2[C:6](=CC=C(OC(F)(F)F)[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]2)[CH:3]=1.C([N:32](CC)CC)C.[N:37]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[C:38]=[O:39].O1[CH2:50][CH2:49][CH2:48][CH2:47]1>>[O:29]=[S:20]1(=[O:28])[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[CH2:23][N:17]([C:4]2[CH:3]=[C:2]([NH:32][C:38]([NH:37][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[O:39])[C:50]3[C:6](=[CH:11][CH:10]=[C:48]([CH3:47])[CH:49]=3)[N:5]=2)[CH2:18][CH2:19]1Participants
Procedure
To a solution of 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine (180 mg, 0.5 mmol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1) and triethylamine (103 mg) in tetrahydrofuran (15 mL) was added a solution of isocyanato-benzene (59.6 mg, 0.5 mmol) in tetrahydrofuran (5 mL) at 0° C. The reaction was stirred at room temperature overnight and then heated at 50° C. for additional 5 hours. The reaction mixture was concentrated in vacuo and the residue was purified by preparative HPLC and SPE to give 17.6 mg of the desired product (yield was 7.5%). MS obsd. (ESI+) [(M+H)+] 473, 1H NMR (400 MHz, CD3OD) δ ppm 8.55 (s, 1 H), 8.12-8.03 (m, 2 H), 7.92 (s, 1 H), 7.86-7.81 (d, J=8.4 Hz, 1 H), 7.76-7.68 (m, 2 H), 7.66-7.57 (m, 3 H), 7.45-7.38 (t, J=7.6 Hz, 2 H), 7.20-7.12 (t, J=2.0 Hz, 1 H), 5.32 (s, 2 H), 4.61-4.40 (m, 2 H), 3.82-3.75 (t, J=2.8 Hz, 2 H), 2.56 (s, 3 H).
Workup
- temperatureheated at 50° C. for additional 5 hours
- concentrationThe reaction mixture was concentrated in vacuo
- customthe residue was purified by preparative HPLC and SPE
Sources & evidence
- ORD record
- ord-6da8051692594ee6bae92d65a802a52a
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08871756B2
Reaction notes
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