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

HRID 2381308Notes

Reaction equation

HRID 2381308 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][C:21]([OH:24])=[CH:20][CH:19]=1.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:21]3[CH:20]=[CH:19][C:18]([C:17]([F:25])([F:26])[F:16])=[CH:23][CH:22]=3)[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 678744-(Trifluoromethyl)phenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 579192623-cyclopentyl-2-[6-oxo-4-(4-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 4-trifluoromethyl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[6-oxo-4-(4-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-propionic acid as a white solid (715.2 mg, 88% for the final step); ES+-HRMS m/e calcd for C19H19N2O4F3 [M+H+] 397.1370, found 397.1371. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.99-1.20 (m, 2H), 1.34-1.79 (m, 7H), 1.91-2.05 (m, 1H), 2.12-2.26 (m, 1H), 5.33 (dd, J=10.8, 4.2 Hz, 1H), 6.01 (d, J=2.9 Hz, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.90 (d, J=8.5 Hz, 2H), 8.14 (d, J=2.9 Hz, 1H), 13.03 (br s, 1H).

Sources & evidence

ORD record
ord-fd533c6cf88a4467978a6bdc48166d4b
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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