Trimethylsilylacetylene → HCID 86700723, compound

HRID 572531Notes

Reaction equation

HRID 572531 reaction equation
C[C:2]([C:11]1[N:12]([CH3:31])[C:13](=[O:30])[C:14]2[C:19]([C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1C)=[CH:18][CH:17]=[C:16](Br)[CH:15]=2)([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[C:3]([OH:5])=[O:4].C[Si]([C:36]#[CH:37])(C)C.[CH3:38]CN(C(C)C)C(C)C>C(#N)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:8][C:7]([O:6][CH:2]([C:11]1[N:12]([CH3:31])[C:13](=[O:30])[C:14]2[C:19]([C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH3:38])[CH:22]=1)=[CH:18][CH:17]=[C:16]([C:36]#[CH:37])[CH:15]=2)[C:3]([OH:5])=[O:4])([CH3:10])[CH3:9]

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 86700724HCID 86700724, compound

Product 1

HCID 86700723HCID 86700723, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl [7-bromo-4-(2,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetic acid (46.0 mg, 0.095 mmol), trimethylsilylacetylene (0.067 mL, 0.473 mmol), copper(I) iodide (3.60 mg, 0.019 mmol) and Hunig's base (0.066 mL, 0.378 mmol) in acetonitrile (1.5 mL) was treated with Pd(PPh3)4 (10.93 mg, 9.46 μmol) and then irradiated in the microwave at 120° C. for 20 minutes. LCMS indicated only 20% conversion to the desired product. N,N-dimethylformamide (DMF) (1.0 mL), trimethylsilylacetylene (0.067 mL, 0.473 mmol) and Pd(PPh3)4 (10.93 mg, 9.46 μmol) were added and the mixture was irradiated in the microwave at 120° C. for 30 minutes. LCMS indicated near complete conversion to the desired product. The mixture was diluted with ethyl acetate and washed successively with saturated sodium sulfate, water, and then brine. The organic phase was dried over sodium sulfate, filtered and concentrated to give a dark residue. The crude residue in tetrahydrofuran (THF) (1.500 mL) was treated with tetrabutylammoniumfluoride (0.142 mL, 0.142 mmol, 1 M solution in THF) at 0° C. and then stirred at ambient temperature for 5 minutes. The mixture was concentrated and purified by reverse phase chromatography to afford the title compound as a tan solid (26 mg, 64%). LC/MS (m/z) ES+=432 (M+1).

Workup

  1. customirradiated in the microwave at 120° C. for 20 minutes

Sources & evidence

ORD record
ord-6d2522dc775e4307a7be1247b33cd6bd
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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