4-((2S)-3-Amino-2-hydroxy-propoxy)-1,3-dihydrobenzoimidazol-2-one → 4-((2S)-2-Hydroxy-3-{1-[4-(2-morpholin-4-yl-4-oxo-4H-thiazol-5-ylidenemethyl)-phenyl]-piperidin-4-ylamino}-propoxy)-1,3-dihydro-benzoimidazol-2-one
Reaction equation
[N:1]1([C:7]2[S:8][C:9](=[CH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[C:10](=[O:12])[N:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH:27][C@@H:28]([CH2:41][NH2:42])[CH2:29][O:30][C:31]1[C:39]2[NH:38][C:37](=[O:40])[NH:36][C:35]=2[CH:34]=[CH:33][CH:32]=1>>[OH:27][C@@H:28]([CH2:41][NH:42][CH:23]1[CH2:22][CH2:21][N:20]([C:17]2[CH:18]=[CH:19][C:14]([CH:13]=[C:9]3[S:8][C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[N:11][C:10]3=[O:12])=[CH:15][CH:16]=2)[CH2:25][CH2:24]1)[CH2:29][O:30][C:31]1[C:39]2[NH:38][C:37](=[O:40])[NH:36][C:35]=2[CH:34]=[CH:33][CH:32]=1Participants
Reactant 2
Product 1
Procedure
The title compound was prepared from 1-[4-(2-morpholin-4-yl-4-oxo-4H-thiazol-5-ylidenemethyl)-phenyl]-piperidin-4-one (which was obtained in Intermediate 28) and (S)-4-[2-hydroxy-3-aminopropoxy]-1,3-dihydro-2H-benzimidazol-2-one (Jesudason, C. D., et al., EP 0 764 640) according to the procedure of Example 1 as a yellowish solid; mp>150° C. (dec.); 1H NMR (300 MHz, DMSO-d6) δ1.20-1-40 (m, 2 H), 1.80-1.95 (m, 2 H), 2.55-2.95 (m, 4 H), 3.60-4.10 (m, 14 H), 4.90 (br s, 1 H), 6.56 (d, J=7.8 Hz, 1 H), 6.62 (d, J=8.0 Hz, 1 H), 6.87 (dd, J=7.9, 7.9 Hz, 1 H), 7.02 (d, J=8.9 Hz, 2 H), 7.45 (d, J=8.9 Hz, 2 H), 7.54 (s, 1 H), 10.65(s, 1 H), 10.75 (brs, 1 H); MS (ES) m/z: 290.0 ((M+2H)2+, 100%); 579.1 (MH+, 80%); HRMS Calcd. for C29H36N6O5S (MH+): 579.2390. Found: 579.2392.
Sources & evidence
- ORD record
- ord-198324668b5e4091a03a11313e1b9369
- Source dataset
- uspto-grants-2002_06
- Patent number
- US06410734B1
Reaction notes
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