تفاعل #76130

معادلة التفاعل

tert-butyl 4-[N-[2-acetoxymethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

NaOH

water

→

tert-Butyl 4-[N-[7-Chloro-2-hydroxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent was removed in vacuo
2. 2
   workup.ADDITIONthe residue was treated with water (35 ml)
3. 3
   استخلاصthe mixture was extracted with ethyl acetate (3×60 ml)
4. 4
   تجفيفdried (Na2SO4)
5. 5
   تركيزconcentrated in vacuo
6. 6
   أخرىPurification by column chromatography
7. 7
   غسيلon elution with 50% ethyl acetate in dichloromethane
8. 8
   أخرىafforded a white solid which
9. 9
   أخرىwas reprecipitated from dichioromethane (minimum amount)/hexanes
10. 10
    ترشيحThe solid was collected by filtration
11. 11
    تجفيفdried in vacuo over P2O5 (0.345 g, 80%), mp 109-111° C.

الإجراء التجريبي

To a solution of tert-butyl 4-[N-[2-acetoxymethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.47 g, 0.92 mmol) in tetrahydrofuran (18 ml), was slowly added 1N aqueous NaOH (1.84 ml, 1.84 mmol) followed by water (1.5 ml). The slightly cloudy solution was stirred at room temperature for 1 hour, the solvent was removed in vacuo and the residue was treated with water (35 ml). The pH was adjusted to 4.5 with 1N HCl and the mixture was extracted with ethyl acetate (3×60 ml). The organics were combined, dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 50% ethyl acetate in dichloromethane, afforded a white solid which was reprecipitated from dichioromethane (minimum amount)/hexanes. The solid was collected by filtration and dried in vacuo over P2O5 (0.345 g, 80%), mp 109-111° C.; 1H-NMR (DMSO-d6); 1.49 (s, 9H, CO2But), 3.50 (s, 3H, N3-Me), 3.25 (s (poorly resolved triplet), 1H, C≡CH), 4.40 (s, 2H, CH2C≡C), 4.57 (d, J=5.70 Hz, 2H, 2-CH2OH), 4.80 (s, 2H, 6-CH2), 5.67 (t, J=6.4 Hz, 1H, CH2OH), 6.78 (d, J=8.80 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.44 Hz, 2H, 2′,6′-Ar), 7.82, 7.87 (2×s, 2H, 5-H, 8-H); MS (FAB, m/z) 467, 469 (M+, 95%, 45% respectively; Cl isotopic pattern).

المصدر