Hydrochloric Acid → 2-Chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

温度

52.5 °C

4-(2-Chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholine VI (27.0 g, 100 mmol) was charged to a suitably sized reactor and tetrahydrofuran (anhydrous, 270 mL) was added. The reaction mixture was cooled to below −10° C., and a 20 wt % solution of i-PrMgCl in tetrahydrofuran (25.7 g, 50.0 mmol) was slowly added, followed by a slow addition of a 25 wt % solution of n-BuLi in heptane (30.0 g, 117 mmol) while an internal temperature below −10° C. was maintained. The mixture was allowed to stir at below −10° C. for 2 h. Anhydrous N,N-dimethylformamide (14.6 g, 200 mmol) was slowly added while keeping the internal temperature below −10° C. The reaction mixture was stirred for 1-2 h, transferred to a mixture of 80% acetic acid, 37% aqueous hydrochloric acid, isopropanol and water. The resulting slurry was heated to 50-55° C. and stirred for 1-3 h. The suspension was concentrated under reduced pressure to remove tetrahydrofuran. The suspension was then cooled to rt, filtered and rinsed with water. The cake was dried under reduced pressure at 40-60° C. to afford 2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde IV as a yellow solid (29.2 g, 98% yield). 1H NMR (400 MHz, CDCl3) δ 10.38 (s, 1H), 4.03-4.05 (m, 4H), 3.85-3.87 (m, 4H), 2.76 (s, 3H)

1. additionwas added
2. temperatureThe reaction mixture was cooled to below −10° C.
3. temperaturewas maintained
4. customthe internal temperature below −10° C
5. stirringThe reaction mixture was stirred for 1-2 h
6. stirringstirred for 1-3 h
7. concentrationThe suspension was concentrated under reduced pressure
8. customto remove tetrahydrofuran
9. temperatureThe suspension was then cooled to rt
10. filtrationfiltered
11. washrinsed with water
12. customThe cake was dried under reduced pressure at 40-60° C.

ORDレコード

ord-9d449beb74214a9c8b9e8b59f63301d2

出典データセット

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08895729B2