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

HRID 1621833노트

반응식

HRID 1621833 반응식
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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-4347fcccff5b479c9a075f229e5ba620
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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