2-Cyclopentyl-6-hydroxy-3,4-dihydroisoquinolin-1(2H)-one → 4-Chloro-3'-((2-cyclopentyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy)methyl)biphenyl-3-carboxylic acid
Reaction equation
[CH:1]1([N:6]2[CH2:15][CH2:14][C:13]3[C:8](=[CH:9][CH:10]=[C:11]([OH:16])[CH:12]=3)[C:7]2=[O:17])[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:19][C:20]1[CH:21]=[C:22]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([C:33]([O:35]C)=[O:34])[CH:27]=2)[CH:23]=[CH:24][CH:25]=1.ClC1C=CC(C2C=CC=C(COC3C=C4C(CCN(C5CCCC5)C4=O)=CC=3)C=2)=CC=1C(O)=O>>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([CH2:19][O:16][C:11]3[CH:12]=[C:13]4[C:8](=[CH:9][CH:10]=3)[C:7](=[O:17])[N:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH2:15][CH2:14]4)[CH:21]=2)=[CH:27][C:28]=1[C:33]([OH:35])=[O:34]Participants
Reactant 3
Product 1
Procedure
2-Cyclopentyl-6-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (0.106 g, 0.5 mmol) and methyl 3′-(bromomethyl)-4-chlorobiphenyl-3-carboxylate (0.208 g, 0.6 mmol) were processed according to the general procedure described for 4-chloro-3′-((2-cyclopentyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl)biphenyl-3-carboxylic acid, to provide 4-chloro-3′-((2-cyclopentyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy)methyl)biphenyl-3-carboxylic acid (0.162 g, 69% over 2 steps) as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 8.00 (s, 1H), 7.87-7.75 (m, 3H), 7.65-7.57 (m, 2H), 7.49-7.41 (m, 2H), 6.95-6.90 (overlapping doublets and singlet, 2H), 5.20 (s, 2H), 4.97-4.93 (m, 1H), 3.34 (t, 2H, J=6.1 Hz), 2.84 (t, 2H, J=6.1 Hz), 1.69-1.46 (m, 8H). LC-MS (ESI) Calcd for C28H26ClNO4 [M+H]+: 476.16. Found: 476.00. HRMS (ESI) calcd for C28H26ClNO4 [M+H]+: 476.1623. Found: 476.1623.
Sources & evidence
- ORD record
- ord-ccc11e8fd70745409b76c2093f57ad4f
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08748632B2
Reaction notes
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