2,5-Difluorophenol → HCID 57919291, compound

HRID 2381335Notes

Reaction equation

HRID 2381335 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][C:20]([F:23])=[CH:19][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[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=3[F:16])[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 949522,5-DifluorophenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 57919291HCID 57919291, compoundYield 59%

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 2,5-difluoro-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2,5-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (10.4 g, 59%) as a white solid; LC-MS 365 [M+H+]; HPLC (0.17% trifluoroacetic acid in acetonitrile/water, 50%-100% acetonitrile, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm), purity>95%. 1H-NMR (300 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.16 (s, 1H), 7.53 (m, 1H), 7.26 (m, 1H), 6.00 (s, 1H), 5.30 (m, 1H), 1.01-2.19 (m, 11H).

Sources & evidence

ORD record
ord-7794f52a97c24b49ba3f4d7d9758f0a3
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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