4,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one → HCID 57919178, compound

HRID 2381346Notes

Reaction equation

HRID 2381346 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[OH:16][C:17]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[CH:20][CH:21]=[N:22]2.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:7]([O:16][C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][CH:21]=[N:22]4)[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 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×HCID 135441757Quinolin-5-ol

Product 1

HCID 57919178HCID 57919178, compoundYield 83%

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 5-hydroxy-quinoline and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[6-oxo-4-(quinolin-5-yloxy)-6H-pyridazin-1-yl]-propionic acid (20 g, 83%) as a solid; LC-MS, [M+H+]=380.2; HPLC (0.17% trifluoroacetic acid in acetonitrile/water, 30%-90% acetonitrile, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm) 254 nm, 95.8%; 214 nm, 99.8%. 1H-NMR (300 MHz, CDCl3): δ 1.12-1.25 (m, 2H), 1.50-1.84 (m, 7H), 2.11-2.20 (m, 1H), 2.33-2.43 (m, 1H), 5.54-5.59 (dd, J=10.5, 4.5 Hz, 1H), 5.94-5.95 (d, J=2.7 Hz, 1H), 7.34-7.37 (d, J=7.8 Hz, 1H), 7.48-7.53 (dd, J=8.7, 4.5 Hz, 1H), 7.74-7.80 (t, 1H), 8.00-8.01 (d, J=3.0 Hz, 1H), 8.14-8.16 (d, J=8.4 Hz, 1H), 8.28-8.31 (d, J=8.4 Hz, 1H), 9.02-9.03 (d, J=3.0 Hz, 1H).

Sources & evidence

ORD record
ord-7139f64c864b4997aac3255ef3502f83
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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