(2,6-Difluorophenyl)acetonitrile → HCID 57919208, compound

HRID 2381366Notes

Reaction equation

HRID 2381366 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6]C=1Cl.[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[CH2:24][C:25]#N.C[O:28][C:29](=[O:38])[CH:30](Br)[CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>>[CH:32]1([CH2:31][CH:30]([N:4]2[C:3](=[O:15])[CH:2]=[C:25]([CH2:24][C:18]3[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:17]=3[F:16])[CH:6]=[N:5]2)[C:29]([OH:28])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

4

Reactant 3

HCID 69559(2,6-Difluorophenyl)acetonitrileHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 57919208HCID 57919208, compoundYield 88%

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 (2,6-difluoro-phenyl)-acetonitrile and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2,6-difluoro-benzyl)-6-oxo-6H-pyridazin-1-yl]-propionic acid (175 mg, 88% for Step 5) as an off-white solid; ES+-HRMS m/e calcd for C20H21N2O3F3 [M+H+] 395.1577, found 395.1576. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91-1.21 (m, 2H), 1.33-1.75 (m, 7H), 1.82-2.04 (m, 1H), 2.07-2.24 (m, 1H), 3.96 (s, 2H), 5.31 (d, J=6.3 Hz, 1H), 6.48 (s, 1H), 7.09-7.25 (m, 2H), 7.37-7.53 (m, 1H), 7.90 (s, 1H), 12.97 (br s, 1H).

Sources & evidence

ORD record
ord-c88106c16aa142a8ba7eba153710e3f8
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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