2-Trifluoromethylphenol → 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-propionic acid

HRID 2381306Notes

Reaction equation

HRID 2381306 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[F:16][C:17]([F:26])([F:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[OH:24].C[O:28][C:29](=[O:38])[CH:30](Br)[CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>>[CH:32]1([CH2:31][CH:30]([N:4]2[C:3](=[O:15])[CH:2]=[C:7]([O:24][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([F:25])([F:26])[F:16])[CH:6]=[N:5]2)[C:29]([OH:28])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

4

Reactant 3

HCID 679582-TrifluoromethylphenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 579191393-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-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-trifluoromethyl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-propionic acid as a white solid (2.74 g, 95% for the final step); ES+-HRMS m/e calcd for C19H19N2O4F3 [M+H+] 397.1370, found 397.1367. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03 (br s, 2H), 1.25-1.77 (m, 7H), 1.88-2.05 (m, 1H), 2.09-2.23 (m, 1H), 5.32 (dd, J=10.6, 3.9 Hz, 1H), 5.92 (d, J=2.4 Hz, 1H), 7.52-7.66 (m, 2H), 7.78-7.94 (m, 2H), 8.17 (d, J=2.4 Hz, 1H), 13.06 (br s, 1H).

Sources & evidence

ORD record
ord-3c690bd066dc4110b1a0238bfaca6817
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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