2,6-Difluorophenol → HCID 57919282, compound

HRID 2381314Notes

Reaction equation

HRID 2381314 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:35])[CH:28](Br)[CH2:29][CH:30]1[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:35])[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 86635176HCID 86635176, compound2×

Product 1

HCID 57919282HCID 57919282, compound

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-cyclobutyl-propionic acid methyl ester (Intermediate 16) afforded 3-cyclobutyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid as a white solid (520.5 mg, 82% for the final step); ES+-HRMS m/e calcd for C17H16N2O4F2 [M+H+] 351.1151, found 351.1152. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44-1.56 (m, 1H), 1.57-1.87 (m, 4H), 1.87-2.01 (m, 1H), 2.03-2.27 (m, 3H), 5.17-5.28 (m, 1H), 6.07 (d, J=2.7 Hz, 1H), 7.32-7.43 (m, 2H), 7.43-7.58 (m, 1H), 8.26 (d, J=2.7 Hz, 1H), 13.05 (br s, 1H).

Sources & evidence

ORD record
ord-24d6b86b617446a186c32f47817b66a6
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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