2-Chloro-4-(trifluoromethoxy)phenol → 5-(2-chloro-4-trifluoromethoxy-phenoxy)-2H-pyridazin-3-one
Reaction equation
I[C:2]1[CH:7]=[N:6][N:5](C2CCCCO2)[C:4](=[O:14])[CH:3]=1.[Cl:15][C:16]1[CH:21]=[C:20]([O:22][C:23]([F:26])([F:25])[F:24])[CH:19]=[CH:18][C:17]=1[OH:27]>>[Cl:15][C:16]1[CH:21]=[C:20]([O:22][C:23]([F:24])([F:25])[F:26])[CH:19]=[CH:18][C:17]=1[O:27][C:2]1[CH:7]=[N:6][NH:5][C:4](=[O:14])[CH:3]=1Participants
Procedure
In an analogous manner to the stepwise sequence outlined in Intermediate 18, starting from 5-iodo-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (Intermediate 18, step 2) and 2-chloro-4-trifluoromethoxy-phenol afforded 5-(2-chloro-4-trifluoromethoxy-phenoxy)-2H-pyridazin-3-one which was then reacted in an analogous manner to that outlined in the synthesis of Intermediate 19 (steps 4 and 5) alkylating with 2-bromo-3-cyclohexyl-propionic acid methyl ester (Intermediate 12) afforded 2-[4-(2-chloro-4-trifluoromethoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclohexyl-propionic acid as a white solid (190 mg, 72% for the final step); ES+-HRMS m/e calcd for C20H20N2O5F3Cl [M+H+] 461.1086, found 461.1085. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.74-1.28 (m, 5H), 1.35-1.80 (m, 6H), 1.80-1.96 (m, 1H), 1.98-2.11 (m, 1H), 5.40 (dd, J=10.9, 4.2 Hz, 1H), 5.95 (d, J=2.7 Hz, 1H), 7.54 (dd, J=9.0, 2.0 Hz, 1H), 7.68 (d, J=9.0 Hz, 1H), 7.87 (d, J=2.0 Hz, 1H), 8.21 (d, J=2.7 Hz, 1H), 13.03 (br. s., 1H).
Sources & evidence
- ORD record
- ord-d0928954e5824689a6f8da529ea2b1e7
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258134B2
Reaction notes
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