Sodium Hydroxide → 7-(2-Methylphenyl)-3-(3-(1,2,3,4-tetrahydronaphthalen-1-yloxy)prop-1-ynyl)-1h-indole-2-carboxylic acid
Reaction equation
[CH:1]1([O:11][CH2:12][C:13]#[C:14][C:15]2[C:23]3[C:18](=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])[CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[C:31]([O:33]CC)=[O:32])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[OH-].[Na+]>O1CCCC1.CO>[CH3:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:18]=1[NH:17][C:16]([C:31]([OH:33])=[O:32])=[C:15]2[C:14]#[C:13][CH2:12][O:11][CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of EXAMPLE 564B (180 mg) and 1-(prop-2-ynyloxy)-1,2,3,4-tetrahydronaphthalene (165 mg) in triethylamine (5 ml) was added bis(triphenylphosphine)palladium(II) dichloride (18.71 mg) and copper(I) iodide (4.23 mg). The reaction mixture was stirred at 70° C. for 3 hours, cooled and concentrated. The residue was dissolved in dichloromethane and purified by flash chromatography, eluting with dichloromethane, to provide ethyl 3-(3-(1,2,3,4-tetrahydronaphthalen-1-yloxy)prop-1-ynyl)-7-o-tolyl-1H-indole-2-carboxylate. This ester was hydrolyzed with aqueous NaOH in tetrahydrofuran and methanol to provide the title compound. 1H NMR (400 MHz, methanol-d4) 7.76 (dd, J=7.98, 1.23 Hz, 1 H), 7.52 (dd, J=6.75, 2.46 Hz, 1 H), 7.34-7.40 (m, 2 H), 7.27-7.31 (m, 2 H), 7.26 (d, J=7.98 Hz, 1 H), 7.13-7.19 (m, 3 H), 7.07-7.12 (m, 1 H), 4.97 (t, J=3.99 Hz, 1 H), 4.52-4.71 (m, 2 H), 2.79-2.90 (m, 1 H), 2.68-2.78 (m, 1 H), 2.14-2.21 (m, 1 H), 2.12 (s, 3 H), 1.91-2.06 (m, 2 H), 1.73-1.84 (m, 1 H).
Sources & evidence
- ORD record
- ord-260663b93d774fd3a59f0f6a28f6dec2
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09035047B2
Reaction notes
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