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

HRID 1811931Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811931
I[C:2]1[C:3]([NH:10][C:11]2[CH:12]=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[CH3:19][C:20]1[N:25]=[C:24]([S:26][CH3:27])[N:23]=[C:22]([Sn](CCCC)(CCCC)CCCC)[N:21]=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>[CH3:9][O:8][C:5]1[N:4]=[C:3]([NH:10][C:11]2[CH:12]=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)[C:2]([C:22]2[N:21]=[C:20]([CH3:19])[N:25]=[C:24]([S:26][CH3:27])[N:23]=2)=[CH:7][N:6]=1

Komponenten

8

Edukt 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 601547172-Methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazineHCID 666002025-iodo-2-methoxy-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

Produkt 1

HCID 666120022-methoxy-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amineAusbeute 69,3 %

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-2-methoxy-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (120 mg, 0.335 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (144 mg, 0.335 mmol), copper(I) iodide (13 mg, 0.067 mmol), cesium fluoride (102 mg, 0.670 mmol), tetrakis(triphenylphosphine)palladium(0) (38.7 mg, 0.034 mmol) and dioxane (2 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 (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as orange solid. The crude product was purified by silica gel chromatography eluting with 60% EtOAc/hexanes to give 2-methoxy-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (86 mg, 0.232 mmol, 69.1% yield). 1H NMR (300 MHz, CDCl3) δ 11.78 (s, 1H); 9.53 (s, 1H); 8.39 (s, 1H); 8.06 (dd, J=8.77, 1.90 Hz, 1H); 6.80 (d, J=8.92 Hz, 1H); 4.01 (s, 3H); 3.96 (s, 3H); 2.63 (s, 6H). m/z (ESI, +ve ion) 372.0 (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 (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as orange solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 60% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-25d6c11b8bf64eeaba53309f6742ee35
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362241B2

Notizen zur Reaktion

Wird geladen…