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

Temperature

-78 °C

5-Chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine (5.1 g, 0.02 mol) was suspended in THF (200 mL) and the resulting solution was cooled to −78° C. whereupon the starting material precipitated from solution. LiHMDS (1M in THF, 25 mL, 1.25 equiv) was added dropwise to the stirred suspension. After addition was complete, the mixture was stirred for 30 min, then DMF (9 mL, 6 equiv) was added and the resulting solution was stirred for 15 min at −78° C. and then warmed to 0° C. and stirred for 15 min. The solution was re-cooled to −78° C. and then cannulated (via a wide-bore double-ended needle) into a stirred solution of ˜0.5M HCl (600 mL). The product precipitated from solution as a pale yellow powder. This was isolated by filtration through a sintered glass funnel, washed with water and dried in vacuo overnight to give 5 g of 5-Chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine-2-carbaldehyde (87.7%). 1H NMR (400 MHz, CDCl3): δ 3.83-3.88 (m, 4 H), 4.06-4.15 (m, 2 H), 4.72 (m, 2 H) and 9.95 (s, 1 H).

1. customprecipitated from solution
2. additionAfter addition
3. stirringthe resulting solution was stirred for 15 min at −78° C.
4. temperaturewarmed to 0° C.
5. stirringstirred for 15 min
6. temperatureThe solution was re-cooled to −78° C.
7. customThe product precipitated from solution as a pale yellow powder
8. customThis was isolated by filtration through a sintered glass funnel
9. washwashed with water
10. customdried in vacuo overnight

ORD record

ord-57f4472a1daf4122bb4cd7d01fb79acb

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394796B2