Potassium Carbonate → HCID 86694439, compound

HRID 1190934Notes

Reaction equation

HRID 1190934 reaction equation
[CH:1]1([C:4]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:5]=2[CH2:6][N:7]2[C:12]3[N:13]=[C:14]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]5[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]5)=[CH:20][CH:19]=4)[N:15]=[CH:16][C:11]=3[CH:10]=[C:9]([C:31]#[C:32]C)[C:8]2=[O:34])[CH2:3][CH2:2]1.C([Si](C)(C)C)#C.C(=O)([O-])[O-].[K+].[K+]>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:1]1([C:4]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:5]=2[CH2:6][N:7]2[C:12]3[N:13]=[C:14]([NH:17][C:18]4[CH:19]=[CH:20][C:21]([N:24]5[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]5)=[CH:22][CH:23]=4)[N:15]=[CH:16][C:11]=3[CH:10]=[C:9]([C:31]#[CH:32])[C:8]2=[O:34])[CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66111TrimethylsilylacetyleneHCID 67997186HCID 67997186, compound

Product 1

HCID 86694439HCID 86694439, compoundYield 19%

Reagents, catalysts & solvents 3

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

Procedure

The mixture of 6-bromo-8-(2-cyclopropyl-6-fluorobenzyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (11, 120 mg, 0.21 mmol), ethynyltrimethylsilane (74 μl, 0.53 mmol), PdCl2(PPh3)2 (15 mg, 0.02 mmol) and CuI (3 mg, 0.02 mmol) in triethylamine (1.5 mL) was irradiated for 90 min at 80° C. in a microwave reactor. The reaction mixture was cooled, filtered through Celite (washed with triethylamine and dichloromethane) and evaporated to dryness. The crude material was purified by column chromatography over silica eluting with chloroform. The isolated material (87 mg) was suspended in 5 mL methanol, potassium carbonate (38 mg, 0.28 mmol) was added and the yellow suspension was stirred for 30 min at room temperature and evaporated. The solid residue was partitioned between water (10 mL) and dichloromethane (2×15 mL). The combined organic layers were washed with brine (15 mL), dried over sodium sulfate, filtered, evaporated and purified by filtration through silica with chloroform:methanol (95:5) followed by preparative HPLC. The title compound (19 mg, 0.04 mmol, 17%) was obtained as a yellow powder. ESMS m/z 509 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.50 (s, 1H) 7.79 (s, 1H) 7.34 (d, J=8.5 Hz, 2H) 7.19 (br. s, 1H) 7.07-7.14 (m, 1H) 6.82-6.92 (m, 3H) 6.78 (dd, J=10.5, 8.8 Hz, 1H) 5.80 (s, 2H) 3.28 (s, 1H) 3.16-3.25 (m, 4H) 2.60-2.69 (m, 4H) 2.39 (s, 3H) 2.16-2.27 (m, 1H) 0.80-0.87 (m, 2H) 0.61-0.68 (m, 2H).

Workup

  1. customwas irradiated for 90 min at 80° C. in a microwave reactor
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through Celite (washed with triethylamine and dichloromethane)
  4. customevaporated to dryness
  5. customThe crude material was purified by column chromatography over silica eluting with chloroform
  6. customevaporated
  7. customThe solid residue was partitioned between water (10 mL) and dichloromethane (2×15 mL)
  8. washThe combined organic layers were washed with brine (15 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. filtrationpurified by filtration through silica with chloroform:methanol (95:5)

Sources & evidence

ORD record
ord-8719698d181b479c98ac7a1c9c48062e
Source dataset
uspto-grants-2014_03
Patent number
US08680099B2

Reaction notes

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