1-Methyl-3-trifluoromethyl-2-pyrazolin-5-one → 3-cyclopentyl-2-[4-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid

HRID 2381391Notes

Reaction equation

HRID 2381391 reaction equation
I[C:2]1[CH:7]=[N:6][N:5](C2CCCCO2)[C:4](=[O:14])[CH:3]=1.[CH3:15][N:16]1[C:20](=[O:21])[CH2:19][C:18]([C:22]([F:25])([F:24])[F:23])=[N:17]1.C[O:27][C:28](=[O:37])[CH:29](Br)[CH2:30][CH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>>[CH:31]1([CH2:30][CH:29]([N:5]2[C:4](=[O:14])[CH:3]=[C:2]([O:21][C:20]3[N:16]([CH3:15])[N:17]=[C:18]([C:22]([F:23])([F:24])[F:25])[CH:19]=3)[CH:7]=[N:6]2)[C:28]([OH:27])=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

4

Reactant 3

HCID 5185661-Methyl-3-trifluoromethyl-2-pyrazolin-5-oneHCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×HCID 579192495-Iodo-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one3×

Product 1

HCID 579191633-cyclopentyl-2-[4-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-6-oxo-6H-pyridazin-1-yl]-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 2-methyl-5-trifluoromethyl-2,4-dihydro-pyrazol-3-one and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid as a white solid (4.3 g, 64% for the final step); LC-MS: 401.1 (M+1)+, tR=4.39 min. Purity on HPLC: 97.0% (214 nm), 99.8% (254 nm), tR=9.36 min. 1H NMR (300 MHz, CDCl3): δ 9.00 (s, 1H), 7.91 (d, 1H), 6.46 (d, 1H, J=2.1 Hz), 6.27 (s, 1H), 5.55 (dd, 1H, J1=7.8 Hz, J2=4.2 Hz,), 3.81 (s, 3H), 2.36˜2.20 (m, 1H), 2.20˜2.05 (m, 1H), 1.78˜1.47 (m, 7H), 1.28˜1.10 (m, 2H).

Sources & evidence

ORD record
ord-709308823dfe48a0ad11cd0e682ec5b6
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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