Triethylamine → 4-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2'-[1,3]dioxolane]

To a stirring solution of 3,5,6,8-tetrahydro-4H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2′-[1,3]dioxolan]-4-one (20.0 g, 0.076 mol) in POCl3 (200 mL) at 0° C. was added triethylamine (200 mL) over a 15 min. period. The resulting mixtures were allowed to warm to rt, and then heated to 80° C. After 3 h, the contents were removed from heating, and allowed to cool to rt. The heterogeneous mixture was concentrated under reduced pressure. The residue was diluted with EtOAc (100 mL), and concentrated again to further remove the volatile materials. The residue was then diluted with EtOAc (100 mL) and the heterogeneous mixture poured onto a stirring mixture of ice-water/aq NaHCO3 (800 mL). After 5 min. stirring, the contents (pH 7) were filtered and the solid filter cake washed with water. The product was dried in vacuum oven overnight to afford the desired product (20.7 g, 97%) as an off-white solid. 1H-NMR (DMSO-d6) δ 8.82 (s, 1H), 3.97 (s, 4H), 3.10 (t, 2H), 3.07 (s, 2H), 1.95 (t, 2H); LCMS RT=2.45 min, [M+H]+=283.1.

1. temperatureheated to 80° C
2. customthe contents were removed
3. temperaturefrom heating
4. temperatureto cool to rt
5. concentrationThe heterogeneous mixture was concentrated under reduced pressure
6. additionThe residue was diluted with EtOAc (100 mL)
7. concentrationconcentrated again
8. customto further remove the volatile materials
9. additionThe residue was then diluted with EtOAc (100 mL)
10. additionthe heterogeneous mixture poured onto a stirring mixture of ice-water/aq NaHCO3 (800 mL)
11. filtrationthe contents (pH 7) were filtered
12. filtrationthe solid filter cake
13. washwashed with water
14. customThe product was dried in vacuum oven overnight

ORD record

ord-86ebc2f67a884915b8e888cdf2328516

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07750017B2