2-Tert-Butylphenol → 2-[4-(2-tert-butyl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid
Reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[OH:26])([CH3:19])([CH3:18])[CH3:17].C[O:28][C:29](=[O:38])[CH:30](Br)[CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>>[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:26][C:7]1[CH:6]=[N:5][N:4]([CH:30]([CH2:31][CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[C:29]([OH:28])=[O:38])[C:3](=[O:15])[CH:2]=1)([CH3:19])([CH3:17])[CH3:18]Participants
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-tert-butyl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 2-[4-(2-tert-butyl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid as a white solid (13.2 g, 81% for the final step); LC-MS 385.2 [M+1]+, tR=5.86 min. Purity on HPLC: 95.7% (214 nm), 88.8% (254 nm), tR=7.87. 1H NMR (300 MHz, CDCl3): δ 10.85 (s, 1H), 7.83 (m, 1H, J=2.4 Hz), 7.44 (d, 1H, J=4.5 Hz), 7.20 (m, 2H), 6.97 (d, 1H, J=7.5 Hz), 6.06 (d, 1H, J=2.4 Hz), 5.36 (dd, 1H, J1=9.6 Hz, J2=4.2 Hz), 2.33˜2.20 (m, 1H), 2.20˜2.05 (m, 1H), 1.66˜1.14 (m, 7H), 1.33 (s, 9H), 1.17˜1.05 (m, 2H).
Sources & evidence
- ORD record
- ord-a957058c976d428aa778f9fdd3ea7711
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258134B2
Reaction notes
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