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

HRID 2381336Notes

Reaction equation

HRID 2381336 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:36])[CH:28](Br)[CH2:29][CH:30]1[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:36])[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 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 579193033-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acidYield 58%

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-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (13.2 g, 58%) as a white solid; ESI-MS 364 [M+H+]; HPLC: >98% (purity). 1H-NMR (300 MHz, CDCl3) δ 7.93-7.94 (d, 1H), 7.22-7.39 (m, 1H), 7.03-7.09 (m, 2H), 6.00 (s, 1H), 5.51-5.56 (m, 1H), 2.29-2.39 (m, 1H), 2.08-2.16 (m, 1H), 1.44-1.81 (m, 7H), 1.10-1.25 (m, 2H).

Sources & evidence

ORD record
ord-f3c8815bac6e4715accc6e1fd8a89691
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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