Ammonia → 5-Pyrimidinecarboxaldehyde, 4-amino-6-chloro-

温度

23 °C

A solution of 7M NH3 in MeOH (265 mL, 1.8602 mol, 2.0 equiv) was added over 1.25 hr to a solution of 4,6-dichloropyrimidine-5-carbaldehyde (9, 163.7 g, 0.9301 mol) in toluene (3 L). The reaction temperature slowly increased from 20 to 26° C. and a yellow suspension formed. Mild cooling was applied to maintain the reaction temperature at <26° C. The suspension was stirred 3.5 hr at room temperature before the solids were collected by filtration. The solids were washed with EtOAc (1 L). The filtrate was concentrated under reduced pressure, and the solids were triturated with toluene/heptane (2:1 v/v, 600 mL), filtered and dried to give 71.1 g of 4-amino-6-chloropyrimidine-5-carbaldehyde (10) as a yellow solid. The original solid filtered from the reaction mixture contained additional 10. The product was extracted from the filtered solid by stirring in EtOAc (1.25 L) for 1.5 hr, filtering, then stirring in THF (750 mL) for 1 hr and filtering. Both EtOAc and THF filtrates were concentrated under reduced pressure, and the resulting solids were triturated with toluene/heptane (2:1 v/v, 450 mL), filtered and dried to give an additional 44.1 g of 4-amino-6-chloropyrimidine-5-carbaldehyde (10) as yellow solids. The combined yield of 4-amino-6-chloropyrimidine-5-carbaldehyde (10, 115.2 g, 146.5 g theoretical) was 78.6%. For 10: 1HNMR (DMSO-d6, 300 MHz) δ ppm 10.23 (s, 1H), 8.71 (bs, 1H), 8.55 (bs, 1H), 8.39 (s, 1H); C5H4ClN3O (MW, 157.56), LCMS (EI) m/e 158 (M++H).

1. customa yellow suspension formed
2. temperatureMild cooling
3. temperatureto maintain the reaction temperature at <26° C
4. filtrationwere collected by filtration
5. washThe solids were washed with EtOAc (1 L)
6. concentrationThe filtrate was concentrated under reduced pressure
7. customthe solids were triturated with toluene/heptane (2:1 v/v, 600 mL)
8. filtrationfiltered
9. customdried

ORDレコード

ord-b301f2984ce649f2b4e510a57396ff77

出典データセット

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08883806B2