Potassium Carbonate → N-(7-(2-chlorophenyl)-5-ethynyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 1502375Notes

Reaction equation

HRID 1502375 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])[CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([NH:19][C:20]([CH:22]1[CH2:24][CH2:23]1)=[O:21])[N:6]=[CH:7]2.C[Si]([C:29]#[CH:30])(C)C.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.CO.ClCCl.[Cu]I.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>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:10]1[CH:9]=[C:8]2[C:3]([CH:4]=[C:5]([NH:19][C:20]([CH:22]3[CH2:24][CH2:23]3)=[O:21])[N:6]=[CH:7]2)=[C:2]([C:29]#[CH:30])[N:11]=1

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 76401542N-(5-chloro-7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

Product 1

HCID 86674952N-(7-(2-chlorophenyl)-5-ethynyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamideYield 50%

Reagents, catalysts & solvents 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of N-(5-chloro-7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide (110 mg, 0.31 mmol), (trimethylsilyl)acetylene (45 mg, 0.46 mmol), N,N-diisopropylethylamine (0.1 mL, 0.61 mmol), copper(I) iodide (6 mg, 0.03 mmol), and bis(triphenylphosphine)palladium(II) chloride (15 mg, 0.02 mmol) in 1,4-dioxane (2 mL) was heated at 50° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was redissolved in methanol (4 mL) and treated with potassium carbonate (210 mg, 1.5 mmol). The reaction mixture was stirred at room temperature for 1 h, and then diluted with dichloromethane (100 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 12 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as a pale yellow solid (50 mg, 50%), which was used in the next step without further purification.

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. washwashed with water (100 mL)
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customto afford a residue that
  14. customwas purified by flash chromatography (silica, 12 g, ISCO, 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6e36e90224c748ad88a8ab8ce45c6792
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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