Triethylamine → HCID 86651993, compound

HRID 1615365Notes

Reaction equation

HRID 1615365 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[NH:4]N=1.[CH3:13]CN(CC)CC.[C:20]([C:22]1[CH:30]=[CH:29][C:25]([N:26]([CH3:28])[CH3:27])=[CH:24][CH:23]=1)#[CH:21]>CN(C=O)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>[CH3:27][N:26]([CH3:28])[C:25]1[CH:29]=[CH:30][C:22]([C:20]#[C:21][C:2]2[C:10]3[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=3)[NH:4][CH:13]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 51918844-Ethynyl-N,N-dimethylanilineHCID 178519327HCID 178519327, compound

Product 1

HCID 86651993HCID 86651993, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-iodo-1H-indazole-6-carbaldehyde (136 mg, 0.5 mmol), Pd(PPh3)2Cl2 (14 mg, 0.02 mmol) and CuI (7.6 mg, 0.04 mmol) in DMF (3 mL) was added Et3N (5 mL), followed by 4-ethynyl-N,N-dimethylaniline (109 mg, 0.75 mmol). The resulting mixture was heated at 100° C. (oil temp.) for 45 min. After removal of Et3N, the residue was loaded directly onto a silical gel column. Flash chromatography (eluent: hex to hex/ethyl acetate=5:1 to 1:1, to ethyl acetate) gave the crude 3-((4-(dimethylamino)phenyl)ethynyl)-1H-indole-6-carbaldehyde as greenish brown solid, which was redissolved in MeOH (20 mL). 2-Oxindole (53.2 mg, 0.4 mmol) and piperidine (10 drops) were added and the resulting mixture was refluxed (oil temp 75° C.) for 2 h. Additional 2-oxindole (13.3 mg) was added and the mixture was refluxed for another hour. After cooling to rt, the reaction mixture was suction filtered and the filter cake was rinsed with MeOH (10 mL). The filtrate was concentrated to about 0.5 mL and diluted with EtOAc (8 mL). Hexane (15 mL) was added and the resulting precipitate was collected by suction filtration to give the title compound (63 mg, 31% over 2 steps) as a golden solid (E:Z=9:1). 1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, br, 1H), 10.64 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.91 (s, 1H), 7.79 (s, 1H), 7.57 (d, J=7.2 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.24 (t, J=7.6 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H), 6.84 (t, J=7.4 Hz, 1H), 6.75 (d, J=8.8 Hz, 2H), 2.97 (s, 6H); MS ESI 405.2 [M+H]+, calcd for [C26H20N4O+H]+ 405.2.

Workup

  1. customAfter removal of Et3N

Sources & evidence

ORD record
ord-c0854550a7b04e60aa010edf1ea30677
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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