Cesium fluoride → 2-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine

HRID 1621516노트

반응식

HRID 1621516 반응식
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[C:5](I)=[CH:4][N:3]=1.[CH3:18][C:19]1[N:24]=[C:23]([S:25][CH3:26])[N:22]=[C:21]([Sn](CCCC)(CCCC)CCCC)[N:20]=1.[F-].[Cs+].O1CCOCC1>O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[C:5]([C:21]2[N:20]=[C:19]([CH3:18])[N:24]=[C:23]([S:25][CH3:26])[N:22]=2)=[CH:4][N:3]=1

참가 물질

8

반응물 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 601547172-Methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazineHCID 866470532-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

생성물 1

HCID 866470542-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine수율 46.4%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매

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온도
140 °C

실험 절차

A glass microwave reaction vessel was charged with 2-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (181 mg, 0.499 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (215 mg, 0.499 mmol), copper(I) iodide (19 mg, 0.100 mmol), cesium fluoride (250 mg, 0.998 mmol), tetrakis(triphenylphosphine)palladium(0) (57.7 mg, 0.050 mmol) and dioxane (3 mL). The reaction mixture was stirred and heated in a Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 30 min. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (10 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 40% EtOAc/hexanes to give 2-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (87 mg, 0.231 mmol, 46.4% yield). 1H NMR (300 MHz, CDCl3) δ 11.82 (s, 1H); 9.48 (s, 1H); 8.37 (s, 1H); 8.08 (dd, J=9.28, 1.97 Hz, 1H); 6.83 (d, J=9.06 Hz, 1H); 3.96 (s, 3H); 2.67 (s, 3H); 2.64 (s, 3H). m/z (ESI, +ve ion) 376.0 (M+H)+.

후처리

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 40% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-e748ac43e6264a3d833eef22869472cf
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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