Acetic Acid → Thieno(3,2-d)pyrimidine-2,4(1H,3H)-dione

To a mixture of methyl 3-amino-thiophenecarboxylate 1 (850 g, 5.41 mol, 1.0 equiv.), acetic acid (6 L) and water (5 L), a solution of potassium cyanate (KOCN, 1316 g, 16.22 mole, 3.0 equiv.) in water (3.2 L) was added slowly over a period of 1 hour. The resulting mixture was stirred at the ambient temperature for 20 hour, filtered and rinsed with water (4 L). The cake was charged to a suitably sized reactor and 2 M aqueous sodium hydroxide solution (14 L) was added. The slurry was stirred for 2 hours and LCMS confirmed the formation of the desired product. The mixture was cooled to 10° C. and 3 M aqueous hydrochloric acid (˜11 L) was added until pH=5.0-6.0 (by pH paper). The slurry was filtered, rinsed with water (6 L), dried in vacuum oven at 50° C. for 24 hours to afford thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione 2 as an off-white solid (834 g, 92%). 1H NMR (400 MHz, DMSO-d6) δ 6.90 (d, J=5.2 Hz, 1H), 8.10 (d, J=5.2 Hz, 1H), 5.40-5.55 (br s, 2H). LCMS (ESI pos) m/e 169 (M+1).

1. filtrationfiltered
2. washrinsed with water (4 L)
3. additionThe cake was charged to a suitably sized reactor and 2 M aqueous sodium hydroxide solution (14 L)
4. additionwas added
5. stirringThe slurry was stirred for 2 hours
6. temperatureThe mixture was cooled to 10° C.
7. addition3 M aqueous hydrochloric acid (˜11 L) was added until pH=5.0-6.0 (by pH paper)
8. filtrationThe slurry was filtered
9. washrinsed with water (6 L)
10. customdried in vacuum oven at 50° C. for 24 hours

ORD record

ord-8e17d221c7e34ec89d64fd4f31fe1868

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354528B2