(1,1'-Biphenyl)-2-ol → 2-[4-(biphenyl-2-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentylpropionic acid

HRID 2381322Notes

Reaction equation

HRID 2381322 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[C:16]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]([OH:22])=[CH:18][CH:19]=[CH:20][CH:21]=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>>[C:16]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][C:7]1[CH:6]=[N:5][N:4]([CH:32]([CH2:33][CH:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)[C:31]([OH:30])=[O:40])[C:3](=[O:15])[CH:2]=1

Participants

4

Reactant 3

HCID 7017(1,1'-Biphenyl)-2-olHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 579191692-[4-(biphenyl-2-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentylpropionic acidYield 75%

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 biphenyl-2-ol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 2-[4-(biphenyl-2-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentylpropionic acid (15.4 g, 75%) as a solid; HPLC (0.17% trifluoroacetic acid in acetonitrile/water, 50%-100% acetonitrile, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm), purity>96% (214 nm). 1H-NMR (CDCl3, 300 MHz) δ0.97-1.10 (m, 2H), 1.45-1.69 (m, 7H), 2.00-2.07 (m, 1H), 2.17-2.22 (m, 1H), 5.39 (dd, J=10.5, 1H), 5.83 (s, 1H), 7.17 (d, J=7.5, 1H), 7.24-7.48 (m, 8H), 7.65 (s, 1H).

Sources & evidence

ORD record
ord-63f79cfbdced424aabb4b1ad4644e856
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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