Reaktion #365024

Reaktionsgleichung

4-amino-3′-chloro-biphenyl-3-carbonitrile

cyclopropylmagnesium bromide

magnesium

cyclopropyl bromide

ammonium chloride

dimethyl carbonate

→

6-(3-chlorophenyl)-4-cyclopropyl-1H-quinazolin-2-one

Ausbeute 18.0%

Lösungsmittel

THF

THF

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigePrepared
2. 2
   workup.ADDITIONAfter addition
3. 3
   Temperaturcooled to ambient temperature
4. 4
   SonstigeThe organic layer was separated
5. 5
   Extraktionthe aqueous layer was extracted with ethyl acetate (3×40 mL)
6. 6
   WaschenThe combined organic layers were washed with brine
7. 7
   Trocknendried with MgSO4
8. 8
   SonstigeAfter removal of the solvent
9. 9
   Sonstigethe residue was purified by a flash chromatography (silica gel, methylene chloride:methanol/25:1)

Vorschrift

Prepared using a similar procedure as described in the literature (Tucker et al. J. Med. Chem., 1994, 37, 2437-2444). To a solution of cyclopropylmagnesium bromide prepared from magnesium (0.9 g, 37 mmol) and cyclopropyl bromide (3.2 mL, 40 mmol) in anhydrous THF was added at 50° C. under nitrogen a solution of 4-amino-3′-chloro-biphenyl-3-carbonitrile (2.3 g, 10 mmol) in anhydrous THF. After addition, the reaction mixture was kept at 50° C. for 30 minutes under nitrogen and treated with dimethyl carbonate in a dropwise manner. The reaction solution was stirred at 50° C. under nitrogen for 30 minutes and cooled to ambient temperature. A saturated aqueous ammonium chloride solution (30 mL) was added followed by addition of ethyl acetate (80 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with brine and dried with MgSO4. After removal of the solvent, the residue was purified by a flash chromatography (silica gel, methylene chloride:methanol/25:1) to give 6-(3-chlorophenyl)-4-cyclopropyl-1H-quinazolin-2-one as a yellowish solid (0.55 g, 18%): mp 189-190° C.; 1H-NMR (DMSO-d6) δ 11.71 (s, 1H, D2O exchangeable), 8.56 (d, 1H, J=1.3 Hz), 8.09 (dd, 1H, J=8.6, 1.6 Hz), 7.92 (s, 1H), 7.77 (d, 1H, J=7.7 Hz), 7.52 (t, 1H, J=7.9 Hz), 7.45 (d, 1H, J=8.1 Hz), 7.36 (d, 1H, J=8.6 Hz), 3.15 (m, 1H), 1.20 (m, 4H); MS (CI) m/z 297 ([M+H]+, 100%); Anal. Calc. For C17H13ClN2O: C, 69.98, H, 4.49, N, 9.23. Found: C, 67.98, H, 4.46, N, 9.10.

Quelle