Potassium Carbonate → Icotinib

HRID 1792760Notes

Reaction equation

HRID 1792760 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:10]3[CH:11]=[C:12]4[O:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][O:22][CH2:21][CH2:20][O:19][C:13]4=[CH:14][C:15]=3[N:16]=[CH:17][N:18]=2)[CH:5]=[CH:6][CH:7]=1.C[Si]([C:33]#[CH:34])(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[C:33]([C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:10]3[CH:11]=[C:12]4[O:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][O:22][CH2:21][CH2:20][O:19][C:13]4=[CH:14][C:15]=3[N:16]=[CH:17][N:18]=2)[CH:5]=[CH:6][CH:7]=1)#[CH:34]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66111TrimethylsilylacetyleneHCID 10216910HCID 10216910, compound2×

Product 1

HCID 22024915IcotinibYield 10.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

(3-Bromo-phenyl)-(7,8,10,11,13,14-hexahydro-6,9,12,15-tetraoxa-1,3-diaza-cyclododeca[b]naphthalen-4-yl)-amine (Compound 10) (10 mg, 0.5 mmol) was dissolved in DMF (10 mL). Tetrakis(triphenylphosphine) palladium (20 mg), trimethylsilylacetylene (70 microliter, 0.65 mmol), potassium carbonate (10 mg) and copper (I) iodide (5 mg) was added under nitrogen atmosphere. The reaction mixture was refluxed for about 3 h and then the reaction cooled and concentrated in vacuo, to afford a residue, which was flash chromotographed to provide a white solid (20 mg). ES-MS m/z 392 (MH+).

Workup

  1. temperatureThe reaction mixture was refluxed for about 3 h
  2. temperaturethe reaction cooled
  3. concentrationconcentrated in vacuo
  4. customto afford a residue, which

Sources & evidence

ORD record
ord-9e262bb65ec44147a7abef9bcbc36b34
Source dataset
uspto-grants-2006_07
Patent number
US07078409B2

Reaction notes

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