2,6-Difluorophenol → HCID 57919133, compound

HRID 2381317Notes

Reaction equation

HRID 2381317 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:37])[CH:28](Br)[CH2:29][CH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[O:24][C:7]1[CH:6]=[N:5][N:4]([CH:28]([CH2:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:27]([OH:26])=[O:37])[C:3](=[O:15])[CH:2]=1

Participants

4

Reactant 3

HCID 943922,6-DifluorophenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57665264Methyl α-bromotetrahydro-2H-pyran-4-propanoate2×

Product 1

HCID 57919133HCID 57919133, 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-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (Intermediate 14) afforded 2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-(tetrahydro-pyran-4-yl)-propionic acid as a white solid (223 mg, 88% for the final step); ES+-HRMS m/e calcd for C18H18N2O5F2 [M+H+] 381.1257, found 381.1257. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.37 (m, 3H), 1.38-1.49 (m, 1H), 1.53-1.68 (m, 1H), 1.86-2.03 (m, 1H), 2.04-2.17 (m, 1H), 3.04-3.29 (m, 2H), 3.70-3.88 (m, 2H), 5.42 (dd, J=10.7, 4.3 Hz, 1H), 6.09 (d, J=2.8 Hz, 1H), 7.33-7.43 (m, 2H), 7.43-7.56 (m, 1H), 8.28 (d, J=2.8 Hz, 1H), 13.13 (br s, 1H).

Sources & evidence

ORD record
ord-323e7dbd4b394405b1997714f1f983e8
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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