N,N-Dimethylaniline → 4-Chloro-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-D]pyrimidin-2-amine

Temperature

110 °C

In a 15 mL flask, 2-amino-6,7,8,9-tetrahydro-1H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one (0.2 g, 0.9 mmol) and tetraethyl ammonium chloride (0.3 g, 1.8 mmol) were dried under vacuum at 100° C. for 12 h. Addition of acetonitrile (1.80 mL), dimethylaniline (0.12 mL, 0.9 mmol) and POCl3 (0.50 mL, 5.42 mmol) followed, and the reaction mixture was heated to 110° C. for 15 min. The solution was concentrated and ice was added along with CHCl3 (5 mL). The aqueous layer pH was adjusted to pH=7 with saturated (satd.) aq. NaHCO3 and extraction from that layer proceeded with CHCl3 (3×20 mL). The combined organic layers were dried (Na2SO4) and concentrated. The resultant residue was purified by FCC (50% EtOAc/hexanes) to afford the desired product as a pale yellow solid (88 mg). Certain substrates were found to be unstable at higher temperatures, in which case prolonged heating at lower temperature (in a range such as from about 50° C. to about 60° C.) sufficed. MS: 240.0. 1H NMR (400 MHz, CDCl3) δ ppm 5.08 (s, 2H), 2.90-2.83 (m, 2H), 2.74-2.67 (m, 2H), 1.98-1.91 (m, 2H), 1.91-1.83 (m, 2H).

1. concentrationThe solution was concentrated
2. additionice was added along with CHCl3 (5 mL)
3. extractionThe aqueous layer pH was adjusted to pH=7 with saturated (satd.) aq. NaHCO3 and extraction from that layer
4. dry with materialThe combined organic layers were dried (Na2SO4)
5. concentrationconcentrated
6. customThe resultant residue was purified by FCC (50% EtOAc/hexanes)

ORD record

ord-065a77a06e4b4413b330c39ec0c82c00

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08193178B2