반응 #76131

ord-d4a7a0d197a6451ba0b505edad115fdf

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    세척washed with 5% aqueous sodium carbonate solution (2×100 ml), brine (100 ml)
  2. 2
    농축concentrated in vacuo
  3. 3
    기타Purification by column chromatography
  4. 4
    세척on gradient elution with methanol in dichloromethane (0 to 2%)
  5. 5
    기타afforded a white crispy solid which
  6. 6
    기타was triturated diethyl ether/hexanes (v/v, 1:2)
  7. 7
    여과The white solid was collected by filtration
  8. 8
    세척washed with hexanes
  9. 9
    건조dried in vacuo over P2O5 (0.202 g, 92%), mp 112-113° C.

실험 절차

To a stirred under argon solution of tert-butyl 4-[N-[7-chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.230 g, 0.42 mmol) in anhydrous dichloromethane (10 ml) was added diethyl amine (0.306 g, 4.2 mmol). The yellow solution was then stirred at room temperature for 18 hours. The solution was then diluted with ethyl acetate (250 ml) and washed with 5% aqueous sodium carbonate solution (2×100 ml), brine (100 ml), and concentrated in vacuo. Purification by column chromatography, on gradient elution with methanol in dichloromethane (0 to 2%) afforded a white crispy solid which was triturated diethyl ether/hexanes (v/v, 1:2). The white solid was collected by filtration, washed with hexanes and dried in vacuo over P2O5 (0.202 g, 92%), mp 112-113° C.; 1H-NMR (DMSO-d6) 0.95 (t, J=6.9 Hz, 6H, 2×CH2CH3), 1.49 (s, 9H, But), 2.56 (q obscured, J=6.85 Hz, 4H, 2×CH2CH3), 3.62 (s, 3H, N3-Me), 3.70 (s, 2H, 2-CH2), 4.40 (s, 2H, CH2C≡C), 4.79 (s, 2H, 6-CH2), 6.78 (d, J=8.9 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.9 Hz, 2′,6′-ArH), 7.81, 7.86 (2×s, 2H, 5-H, 8-H); MS (FAB, m/z) 523, 525 [(M+H)+, 100%, 40% respectively; Cl isotopic pattern].

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06699861B1uspto-grants-2004_03