3-Chloro-2-fluorophenol → 2-[4-(3-chloro-2-fluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid

HRID 2381392Notes

Reaction equation

HRID 2381392 reaction equation
I[C:2]1[CH:7]=[N:6][N:5](C2CCCCO2)[C:4](=[O:14])[CH:3]=1.[Cl:15][C:16]1[C:17]([F:23])=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1.C[O:25][C:26](=[O:35])[CH:27](Br)[CH2:28][CH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>>[Cl:15][C:16]1[C:17]([F:23])=[C:18]([CH:19]=[CH:20][CH:21]=1)[O:22][C:2]1[CH:7]=[N:6][N:5]([CH:27]([CH2:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[C:26]([OH:25])=[O:35])[C:4](=[O:14])[CH:3]=1

Participants

4

Reactant 3

HCID 27737123-Chloro-2-fluorophenolHCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×HCID 579192495-Iodo-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one3×

Product 1

HCID 579193202-[4-(3-chloro-2-fluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid

Procedure

In an analogous manner to the stepwise sequence outlined in Intermediate 70, starting from 5-iodo-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (Intermediate 70 step 2) and 3-chloro-2-fluoro-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 2-[4-(3-chloro-2-fluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid as a white solid (4.4 g, 73% for the final step); LC-MS: tR=4.80 min, 381 (M+H)+. HPLC: tR=8.83 min, 95.66% (214 nm), 95.56% (254 nm). 1H NMR (300 MHz, DMSO-d6): δ 13.06 (broad, 1H), 8.21 (d, 1H, J=2.7 Hz), 7.63-7.58 (m, 1H), 7.54-7.49 (m, 1H), 7.38-7.33 (m, 1H), 6.07 (d, 1H, J=2.7 Hz), 5.33 (dd, 1H, J=11.0 Hz, J=4.2 Hz), 2.40-2.10 (m, 1H), 1.99-1.90 (m, 1H), 1.68-1.43 (m, 7H), 1.13-1.04 (m, 2H).

Sources & evidence

ORD record
ord-7a45b56e3f3342a2a773db4814fe35cf
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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