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

HRID 1621527Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1621527
I[C:2]1[C:3]([NH:13][C:14]2[CH:15]=[N:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)=[N:4][C:5]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH3:22][C:23]1[N:28]=[C:27]([S:29][CH3:30])[N:26]=[C:25]([Sn](CCCC)(CCCC)CCCC)[N:24]=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>[CH3:21][O:20][C:17]1[N:16]=[CH:15][C:14]([NH:13][C:3]2[C:2]([C:25]3[N:24]=[C:23]([CH3:22])[N:28]=[C:27]([S:29][CH3:30])[N:26]=3)=[CH:7][N:6]=[C:5]([N:8]3[CH2:12][CH2:11][CH2:10][CH2:9]3)[N:4]=2)=[CH:19][CH:18]=1

Komponenten

8

Edukt 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 601547172-Methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazineHCID 666002845-iodo-N-(6-methoxypyridin-3-yl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine

Produkt 1

HCID 66611957N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-2-(pyrrolidin-1-yl)pyrimidin-4-amineAusbeute 19,22 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A glass microwave reaction vessel was charged with 5-iodo-N-(6-methoxypyridin-3-yl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (141 mg, 0.355 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (153 mg, 0.355 mmol), copper(I) iodide (14 mg, 0.071 mmol), cesium fluoride (108 mg, 0.710 mmol), tetrakis(triphenylphosphine)palladium(0) (41.0 mg, 0.035 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 (10 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 brown oil. The crude product was purified by silica gel chromatography eluting with 60% EtOAc/hexanes to give N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (28 mg, 0.068 mmol, 19.22% yield). 1H NMR (300 MHz, CDCl3) δ 11.74 (s, 1H); 9.45 (s, 1H); 8.49 (s, 1H); 8.13 (dd, J=8.92, 2.34 Hz, 1H); 6.77 (d, J=8.77 Hz, 1H); 3.95 (s, 3H); 3.58-3.76 (m, 4H); 2.59 (s, 3H); 2.57 (s, 3H); 1.93-2.09 (m, 4H). m/z (ESI, +ve ion) 411.0 (M+H)+.

Aufarbeitung

  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 brown oil
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 60% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-2c70c86fd84446debee73b03fc3041b6
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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