反应详情

A 50 mL 3-necked flask fitted with a thermometer was charged with 1,4-dioxane (20 mL) and 4,5-dichloropyrimdine-5-amine (5.00 g, 30.5 mmol). The reaction mixture was then stirred for 30 minutes at room temperature to ensure complete dissolution of the 4,5-dichloropyrimidine-5-amine, after which a solution of methylamine in water (40% by weight, 120 mmol, 9.3 mL) was added over a period of 30 minutes by means of a pressure-equalized dropping funnel. Upon completion of addition, the dropping funnel was replaced with a reflux condenser. The stirred reaction mixture was then heated to 75° C. over a period of 40 minutes, and the progress was monitored by LCMS. The reaction was complete after 16 hours. The resulting mixture was then cooled to 50° C. and poured into 120 mL of ice and water (approximetely 1:1 by volume), which resulted in the rapid precipitation of a solid. The resulting suspension was then for a period of 2 hours. The precipitated solids were collected by vacuum filtration, washed with ice-cold water (20 mL) and dried on the filter to give 4.76 g (98.4% yield) of 6-chloro-N4-methylpyrimidine-4,5-diamine as a light yellow solid. This material was submitted to the next step without further purification. 1H-NMR (400 MHz, DMSO-d6): δ 7.73 (s, 1H), 6.87 (d, 1H), 4.94 (broad s, 2H), 2.86 (d, 3H). MS (EI) for C5H7ClN4: 159 (MH+).

1. customA 50 mL 3-necked flask fitted with a thermometer
2. additionUpon completion of addition
3. customthe dropping funnel was replaced with a reflux condenser
4. customThe stirred reaction mixture
5. temperaturewas then heated to 75° C. over a period of 40 minutes
6. waitThe reaction was complete after 16 hours
7. temperatureThe resulting mixture was then cooled to 50° C.
8. customresulted in the rapid precipitation of a solid
9. waitfor a period of 2 hours
10. filtrationThe precipitated solids were collected by vacuum filtration
11. washwashed with ice-cold water (20 mL)
12. customdried on the
13. filtrationfilter