3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid → N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionamide
Reaction equation
[CH:1]1([CH2:7][CH:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([O:19][C:20]3[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=3[F:27])[CH:14]=[N:13]2)[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28]([Si:32]([CH3:43])([CH3:42])[O:33][CH2:34][CH2:35][N:36]1[CH:40]=[CH:39][C:38]([NH2:41])=[N:37]1)([CH3:31])([CH3:30])[CH3:29]>>[C:28]([Si:32]([CH3:43])([CH3:42])[O:33][CH2:34][CH2:35][N:36]1[CH:40]=[CH:39][C:38]([NH:41][C:9](=[O:10])[CH:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([O:19][C:20]3[C:21]([F:27])=[CH:22][CH:23]=[CH:24][C:25]=3[F:26])[CH:14]=[N:13]2)[CH2:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[N:37]1)([CH3:31])([CH3:30])[CH3:29]Participants
Reactant 2
Product 1
Procedure
Using the method described in Example 49, 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 33) and 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-ylamine (Intermediate 3) afforded N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionamide as a white solid (1.42 g, 65%); ES+-HRMS m/e calcd for C30H41N5O4SiF2 [M+H+] 602.2969 found 602.2971. 1H NMR (300 MHz, DMSO-d6) δ ppm −0.07 (s, 6H) 0.80 (s, 9H) 0.84-1.30 (m, 6H) 1.63 (br s, 5H) 1.75-1.92 (m, 1H) 2.04-2.21 (m, 1H) 3.85 (t, J=5.1 Hz, 2H) 4.06 (t, J=5.1 Hz, 2H) 5.54 (dd, J=10.7, 4.1 Hz, 1H) 6.03 (d, J=2.7 Hz, 1H) 6.36 (d, J=2.1 Hz, 1H) 7.33-7.52 (m, 3H) 7.53 (d, J=2.1 Hz, 1H) 8.28 (d, J=2.7 Hz, 1H) 10.73-10.91 (m, 1H).
Sources & evidence
- ORD record
- ord-6c0db8ff717f46b89271cdab830dbddb
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258134B2
Reaction notes
Loading…