Hydrochloric Acid → 5-Chloro-7-morpholinothiazolo[4,5-d]pyrimidine-2-carbaldehyde

Temperature

-78 °C

To a suspension of 5-chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidine (2 g, 7.79 mmol) in anhydrous tetrahydrofuran, cooled to −78° C. under nitrogen atmosphere, lithium bis(trimethylsilyl)amide (11.7 mL, 11.68 mmol) was added dropwise at −78° C. and the resulting reaction mixture stirred at −78° C. for 1 h. Subsequently DMF was slowly added and the mixture stirred for further 30 min. The temperature was allowed to rise to −5° C. over 10 min and then cooled again to −78° C. The resulting reaction mixture was transferred via cannula into ice-cold aqueous 1M HCl (400 mL) and stirred vigorously. The aqueous phase was extracted with ethyl acetate (2×150 mL). The organic layer was washed with water (1×125 mL), brine (2×125 mL), dried over Na2SO4 and filtered. The solvent was reduced in vacuo to afford the title compound as an orange-brown solid (1.82 g, 82%). 1H NMR (400 MHz, CDCl3): δ 10.19 (1 H, s), 4.03 (4 H, t, J=4.90 Hz), 3.87 (4 H, t, J=4.90 Hz).

1. customthe resulting reaction mixture
2. stirringthe mixture stirred for further 30 min
3. waitto rise to −5° C. over 10 min
4. temperaturecooled again to −78° C
5. customThe resulting reaction mixture
6. stirringstirred vigorously
7. extractionThe aqueous phase was extracted with ethyl acetate (2×150 mL)
8. washThe organic layer was washed with water (1×125 mL), brine (2×125 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered

ORD record

ord-703b5939c40c4afbbf48799f0efee686

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173650B2