反应 #2075722

反应方程式

ammonia

ammonia

2,6-Dichloro-5-methoxypyrimidine-4-carboxylic acid methyl ester

ammonia

→

title compound

收率 29.0%

6-Amino-2-chloro-5-methoxypyrimidine-4-carboxylic acid methyl ester

收率 29.0%

溶剂

methanol

methanol

chloroform

methanol

反应条件

后处理

1. 1
   workup.STIRRINGThe reaction was stirred at ambient temperature for 16 h
2. 2
   workup.STIRRINGThe reaction was stirred for 2 h during which time a solid
3. 3
   其他precipitated
4. 4
   过滤The solid was filtered off
5. 5
   workup.ADDITIONwater was added to the filtrate
6. 6
   萃取The crude material was extracted from the filtrate with dichloromethane three times
7. 7
   洗涤the combined organic phases were washed with brine
8. 8
   其他dried
9. 9
   浓缩concentrated under vacuum
10. 10
    其他The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

实验过程

2,6-Dichloro-5-methoxypyrimidine-4-carboxylic acid methyl ester (750 mg, 3.16 mmol; see J. Med. Chem. 49(5), 1693-1705; 2006 for preparation) was dissolved in chloroform and 2N ammonia in methanol (2 eq) was added dropwise while in a cooling bath. The reaction mixture was stirred for 30 min, after which an additional 2 eq of 2N ammonia in methanol was added. The reaction was stirred at ambient temperature for 16 h. Additional 2N ammonia in methanol (2 eq) was added. The reaction was stirred for 2 h during which time a solid precipitated. The solid was filtered off and water was added to the filtrate. The crude material was extracted from the filtrate with dichloromethane three times and the combined organic phases were washed with brine, dried and concentrated under vacuum. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to provide the title compound (202 mg, 29% yield): mp 162-167° C.; 1HNMR (CDCl3): δ 5.75 (br s, 2H), 3.97 (s, 3H), 3.92 (s, 3H).

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