HCID 68939125, compound → Ethyl 3-(3-(1,2,3,4-tetrahydronaphthalen-1-yloxy)prop-1-ynyl)-7-o-tolyl-1h-indole-2-carboxylate

HRID 2095285Notes

Reaction equation

HRID 2095285 reaction equation
I[C:2]1[C:10]2[C:5](=[C:6]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH3:17])[CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19].[CH2:23]([O:26][CH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][CH2:28]1)[C:24]#[CH:25]>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH:27]1([O:26][CH2:23][C:24]#[C:25][C:2]2[C:10]3[C:5](=[C:6]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[CH3:17])[CH:7]=[CH:8][CH:9]=3)[NH:4][C:3]=2[C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 2

HCID 68939125HCID 68939125, compoundHCID 846179381-(Prop-2-ynyloxy)-1,2,3,4-tetrahydronaphthalene

Product 1

HCID 68939063Ethyl 3-(3-(1,2,3,4-tetrahydronaphthalen-1-yloxy)prop-1-ynyl)-7-o-tolyl-1h-indole-2-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

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, 1H), 7.52 (dd, J=6.75, 2.46 Hz, 1H), 7.34-7.40 (m, 2H), 7.27-7.31 (m, 2H), 7.26 (d, J=7.98 Hz, 1H), 7.13-7.19 (m, 3H), 7.07-7.12 (m, 1H), 4.97 (t, J=3.99 Hz, 1H), 4.52-4.71 (m, 2H), 2.79-2.90 (m, 1H), 2.68-2.78 (m, 1H), 2.14-2.21 (m, 1H), 2.12 (s, 3H), 1.91-2.06 (m, 2H), 1.73-1.84 (m, 1H).

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in dichloromethane
  4. custompurified by flash chromatography
  5. washeluting with dichloromethane

Sources & evidence

ORD record
ord-da2247afdeba43c2a4a73a601573ea39
Source dataset
uspto-grants-2013_05
Patent number
US08445679B2

Reaction notes

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