Ammonia → 2-(Chloromethyl)quinazoline
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[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]=O)=O.[NH3:14].CO>C(Cl)(Cl)Cl.CCCCCC.CCOC(C)=O>[Cl:1][CH2:2][C:3]1[N:14]=[CH:12][C:7]2[C:6](=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=1[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]=O)=O.[NH3:14].CO>C(Cl)(Cl)Cl.CCCCCC.CCOC(C)=O>[Cl:1][CH2:2][C:3]1[N:14]=[CH:12][C:7]2[C:6](=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=1The product of the first step, 2-chloro-N-(2-formylphenyl)acetamide (0.869 g, 4.40 mmol) and ammonia, 7N solution in methanol (4.4 mL, 30.8 mmol) were stirred together at ambient in a sealed tube for 4.5 hours. A TLC (9:1 hexane EtOAc) check indicated that a new lower Rf spot had formed, however, plenty of starting material remained so stirring at ambient temperature was continued for another 19.5 hours, during which time a white precipitate had formed. Volatiles were removed under reduced pressure to give a beige solid that was treated with CHCl3. The portion that was soluble was checked by TLC (7:3 hexane/EtOAc). The major spot in the CHCl3-soluble portion was a new one with lower Rf than the starting material. The CHCl3 mixture was placed in the 0° C. freezer over the weekend. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on an Analogix IF-280 (Agilent SF10-4 g, 100% CHCl3). The product eluted in fractions #1-10. The product fractions were combined and concentrated under reduced pressure to give 2-(chloromethyl)quinazoline as a white solid (418 mg, 53.2%). 1H NMR (300 MHz, CDCL3) δ 9.45 (s, 1H), 8.09 8.04 (m, 1H), 7.99-7.92 (m, 2H), 7.70 (ddd, J=8.0, 6.9, 1.2 Hz, 1H), 4.92 (s, 2H).
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