2,6-Difluorophenol → 2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-phenyl-propionic acid

HRID 2381315Notes

Reaction equation

HRID 2381315 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[OH:24].C[O:26][C:27](=[O:37])[CH:28](Br)[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[O:24][C:7]1[CH:6]=[N:5][N:4]([CH:28]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:27]([OH:26])=[O:37])[C:3](=[O:15])[CH:2]=1

Participants

4

Reactant 3

HCID 943922,6-DifluorophenolHCID 10538169Methyl 2-bromo-3-phenylpropanoate2×HCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×

Product 1

HCID 579192212-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-phenyl-propionic acid

Procedure

In an analogous manner to the stepwise sequence outlined in intermediate 19, starting from 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20) and 2,6-difluoro-phenol and alkylating with 2-bromo-3-phenyl-propionic acid methyl ester (Intermediate 13) afforded 2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-phenyl-propionic acid as a white solid (555.8 mg, 96% for the final step); ES+-HRMS m/e calcd for C19H14N2O4F2 [M+H+] 373.0995, found 373.0994. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.28-3.37 (m, 1H), 3.44 (dd, J=14.3, 4.7 Hz, 1H), 5.64 (dd, J=11.1, 4.7 Hz, 1H), 5.96 (d, J=2.7 Hz, 1H), 7.09-7.25 (m, 5H), 7.30-7.41 (m, 2H), 7.41-7.52 (m, 1H), 8.19 (d, J=2.7 Hz, 1H), 13.24 (br s, 1H).

Sources & evidence

ORD record
ord-bcd6e3977f8947bc93c4cb85862409cc
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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