2-Chloro-4-methoxyphenol → 5-(2-chloro-4-methoxy-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][CH3:23])[CH:19]=[CH:18][C:17]=1[OH:24]>>[Cl:15][C:16]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=1[O:24][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-methoxy-phenol afforded 5-(2-chloro-4-methoxy-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) which afforded the lithium salt of 2-[4-(2-chloro-4-methoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclohexyl-propionic acid as a white solid (0.19 g); ES+-HRMS m/e calcd for C20H23N2O5Cl [M+H+] 407.1368, found 407.1369. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.68-1.19 (m, 6H), 1.44-1.65 (m, 4H), 1.65-1.77 (m, 1H), 1.93 (t, J=6.9 Hz, 2H), 3.81 (s, 3H), 5.09 (t, J=7.7 Hz, 1H), 5.52 (d, J=3.0 Hz, 1H), 7.04 (dd, J=9.0, 3.0 Hz, 1H), 7.26 (d, J=3.0 Hz, 1H), 7.39 (d, J=9.0 Hz, 1H), 7.97 (d, J=3.0 Hz, 1H).
Sources & evidence
- ORD record
- ord-a186a634b66345fda6806bbe3831da82
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258134B2
Reaction notes
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