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

HRID 2381318Notes

Reaction equation

HRID 2381318 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][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH:30]1([CH2:29][CH:28]([N:4]2[C:3](=[O:15])[CH:2]=[C:7]([O:24][C:18]3[C:17]([F:16])=[CH:22][CH:21]=[CH:20][C:19]=3[F:23])[CH:6]=[N:5]2)[C:27]([OH:26])=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

4

Reactant 3

HCID 943922,6-DifluorophenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 579191702-Bromo-3-cyclohexyl-propionic acid methyl ester2×

Product 1

HCID 579193023-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-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-cyclohexyl-propionic acid methyl ester (Intermediate 12) afforded 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid as a white solid (1.3 g, 99% for the final step); ES+-HRMS m/e calcd for C19H20N2O4F2 [M+H+] 379.1464, found 379.1463. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.63-1.31 (m, 6H) 1.33-2.19 (m, 7H) 5.38 (dd, J=10.9, 3.9 Hz, 1H) 6.08 (br s, 1H) 7.24-7.56 (m, 3H) 8.26 (d, J=2.7 Hz, 1H) 13.11 (br s, 1H).

Sources & evidence

ORD record
ord-f72311ce194143948b2a9eff58115d59
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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