Cesium fluoride → 1-(5-(6-Methoxypyridin-3-ylamino)-6-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)ethanone

HRID 1621833Notes

Reaction equation

HRID 1621833 reaction equation
Cl[C:2]1[N:3]=[C:4]([C:17]2[CH:22]=[C:21]([S:23][CH3:24])[N:20]=[C:19]([CH3:25])[N:18]=2)[C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[F-].[Cs+].C([Sn](CCCC)(CCCC)[C:67]([O:69]CC)=[CH2:68])CCC>O1CCOCC1.O.[Cu]I.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([NH:8][C:5]2[N:6]=[CH:7][C:2]([C:67](=[O:69])[CH3:68])=[N:3][C:4]=2[C:17]2[CH:22]=[C:21]([S:23][CH3:24])[N:20]=[C:19]([CH3:25])[N:18]=2)=[CH:14][CH:13]=1

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866470685-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine

Product 1

HCID 666003381-(5-(6-Methoxypyridin-3-ylamino)-6-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)ethanoneYield 62.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine (30 mg, 0.080 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-triisopropyl-biphenyl (7.63 mg, 0.016 mmol, Aldrich), copper (I) iodide (17 mg, 0.016 mmol, Aldrich), palladium diacetate (1.8 mg, 8.00 μmol, Aldrich), cesium fluoride (15 mg, 0.160 mmol, Alfa Aesar) and tributyl(1-ethoxyvinyl)tin (0.041 mL, 0.120 mmol, Aldrich) in dioxane (2 mL) was stirred at 100° C. for 18 h. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography, eluting with 10% EtOAc/CH2Cl2 to give 1-(5-(6-methoxypyridin-3-ylamino)-6-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)ethanone (19 mg, 0.050 mmol, 62.1% yield). 1H NMR (300 MHz, CDCl3) δ 2.66 (s, 3H) 2.71 (s, 3H) 2.80 (s, 3H) 3.96 (s, 3H) 6.82 (d, J=8.92 Hz, 1H) 8.14 (dd, J=8.92, 2.78 Hz, 1H) 8.25 (s, 1H) 8.45 (d, J=2.63 Hz, 1H) 8.91 (s, 1H) 12.79 (s, 1H). m/z (ESI, +ve ion) 383.0 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. washThe combined organic extracts were washed with saturated NaCl (5 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customto give the crude material as a yellow solid
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with 10% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-4347fcccff5b479c9a075f229e5ba620
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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