반응 #2075722

반응 방정식

ammonia

ammonia

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

ammonia

→

title compound

수율 29.0%

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

수율 29.0%

용매

methanol

methanol

chloroform

methanol

반응 조건

후처리

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
   기타precipitated
4. 4
   여과The solid was filtered off
5. 5
   workup.ADDITIONwater was added to the filtrate
6. 6
   추출The crude material was extracted from the filtrate with dichloromethane three times
7. 7
   세척the combined organic phases were washed with brine
8. 8
   기타dried
9. 9
   농축concentrated under vacuum
10. 10
    기타The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

실험 절차

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).

출처