m-Trifluoromethylphenylacetonitrile → HCID 57919155, compound

HRID 2381365Notes

Reaction equation

HRID 2381365 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6]C=1Cl.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:19]=[C:20]([CH2:24][C:25]#N)[CH:21]=[CH:22][CH:23]=1.C[O:30][C:31](=[O:40])[CH:32](Br)[CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>>[CH:34]1([CH2:33][CH:32]([N:4]2[C:3](=[O:15])[CH:2]=[C:25]([CH2:24][C:20]3[CH:21]=[CH:22][CH:23]=[C:18]([C:17]([F:28])([F:27])[F:16])[CH:19]=3)[CH:6]=[N:5]2)[C:31]([OH:30])=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

4

Reactant 3

HCID 75360m-TrifluoromethylphenylacetonitrileHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 57919155HCID 57919155, compoundYield 70%

Procedure

In an analogous manner to the stepwise sequence outlined in Intermediate 63, starting from 4,5-dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (Intermediate 20) and (3-trifluoromethyl-phenyl)acetonitrile and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[6-oxo-4-(3-trifluoromethyl-benzyl)-6H-pyridazin-1-yl]-propionic acid (200.1 mg, 70% for Step 5) as a yellow solid; ES+-HRMS m/e calcd for C20H21N2O3F3 [M+H+] 395.1577, found 395.1576. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.99 (br s, 2H), 1.30-1.78 (m, 7H), 1.83-2.05 (m, 1H), 2.07-2.24 (m, 1H), 3.99 (s, 2H), 5.31 (dd, J=10.6, 4.2 Hz, 1H), 6.73 (s, 1H), 7.50-7.69 (m, 3H), 7.73 (s, 1H), 7.95 (d, J=1.8 Hz, 1H), 12.97 (br s, 1H).

Sources & evidence

ORD record
ord-1d2befe2981c45a4978f67610ab2003d
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

Loading…