2-(Pyrrolidin-1-yl)phenol → 3-cyclopentyl-2-[6-oxo-4-(2-pyrrolidin-1-yl-phenoxy)-6H-pyridazin-1-yl]propionic acid
Reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[N:16]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[OH:27])[CH2:20][CH2:19][CH2:18][CH2:17]1.C[O:29][C:30](=[O:39])[CH:31](Br)[CH2:32][CH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>>[CH:33]1([CH2:32][CH:31]([N:4]2[C:3](=[O:15])[CH:2]=[C:7]([O:27][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[CH:6]=[N:5]2)[C:30]([OH:29])=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34]1Participants
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 2-pyrrolidin-1-yl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[6-oxo-4-(2-pyrrolidin-1-yl-phenoxy)-6H-pyridazin-1-yl]propionic acid (9 g, 57%) as a yellow solid; LC-MS 398 [M+H+]; HPLC [acetonitrile (0.1% trifluoroacetic acid) in water (0.1% trifluoroacetic acid)=100%˜50%, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm], 254 nm, 97%, 214 nm, 96%. 1H-NMR (300 MHz, CDCl3): δ 7.82 (s, 1H), 7.15 (t, J=7.2 Hz, 1H), 6.95 (d, J=7.5 Hz, 1H), 6.75-6.82 (m, 2H), 5.92 (s, 1H), 5.49 (s, 1H), 3.25 (s, 4H), 2.31 (s, 1H), 2.15 (s, 1H), 1.25-1.87 (m, 11H), 1.08-1.16 (m, 2H).
Sources & evidence
- ORD record
- ord-4ed8301218b54736b218ded01d373483
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258134B2
Reaction notes
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