Dimethylformamide → 2-Amino-4-chloro-6-cyano-pyrimidylacetate-t-butyl ester

反応式

[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])#N.[NH2:13][C:14]1[N:19]=[C:18]([Cl:20])[CH:17]=[C:16](Cl)[N:15]=1.C[N:23](C)C=O>>[C:9]([O:8][C:6](=[O:7])[CH2:5][C:3]1[C:18]([Cl:20])=[N:19][C:14]([NH2:13])=[N:15][C:16]=1[C:17]#[N:23])([CH3:12])([CH3:11])[CH3:10]

参加物

反応物 4

HCID 6228Dimethylformamide

HCID 24758Sodium hydride

HCID 655222-Amino-4,6-dichloropyrimidine

HCID 70693tert-Butyl cyanoacetate

生成物 1

HCID 539121792-Amino-4-chloro-6-cyano-pyrimidylacetate-t-butyl ester

反応条件

温度: 0 °C

実験手順

To a suspension of sodium hydride (17.6 g, 733 mmol) in dry N,N-dimethylformamide (DMF) at 0° C. was added dropwise t-butyl cyanoacetate (96 g, 680 mmol). The tan suspension was stirred at 0° C. for 0.5 hours then 2-amino-4,6-dichloropyrimidine (58.7 g, 358 mmol) was added batchwise. The mixture was heated slowly to 90° C. and the reaction was held at 90° C. for 18 hours. The reaction mixture was poured onto water (1 l) and the mixture was filtered. The filtrate was acidified with con HCl to pH 6 and the resultant solid was filtered and washed with water and hexanes and dried to furnish 99.64 g of the desired subject as a green powder, m.p. 107°-109° C. NMR (200 mHz) D6-acetone δ 12.8 (bs, 1 H), 8.0 (bs, 1 H), 7.8 (bs, 1 H), 6.3 (s, 1 H), 1.5 (s, 9 H).