Methyl iodide → 4-(4-chlorophenyl)-2-iodo-7-methyl-4,5,6,7-tetrahydro-8H-thieno[2,3-e]azepin-8-one

Temperature

-78 °C

To a solution of 4-(4-chlorophenyl)-2-iodo-4,5,6,7-tetrahydro-8H-thieno[2,3-c]azepin-8-one (95.0 mg, 0.235 mmol, prepared in an analogous manner as described in Example 33) in tetrahydrofuran (8.6 mL) at −78° C. under an atmosphere of argon was added LiHMDS in hexane (1 M, 0.259 mL, 0.259 mmol). After stirring at −78° C. for 5 min, methyl iodide (0.293 mL, 4.70 mmol) was added and the resulting yellow solution was stirred at rt for 16 hr. The mixture was quenched with saturated NH4Cl aqueous solution, the volatiles were removed and the obtained residue was purified by silica gel column chromatography (elution with 0-50% EA/hexane) to give the title compound as a white solid (52.8 mg, 53% yield). LCMS: (FA) ES+ , 417/419. 1H NMR (300 MHz, DMSO) δ 7.37 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H), 6.75 (d, J=11.3 Hz, 1H), 4.36 (dt, J=30.3, 15.3 Hz, 1H), 3.59-3.34 (m, 2H), 3.03 (d, J=8.8 Hz, 3H), 2.38-2.15 (m, 1H), 2.12-1.92 (m, 1H).

1. customat −78° C.
2. stirringthe resulting yellow solution was stirred at rt for 16 hr
3. customThe mixture was quenched with saturated NH4Cl aqueous solution
4. customthe volatiles were removed
5. customthe obtained residue was purified by silica gel column chromatography (elution with 0-50% EA/hexane)

ORD record

ord-9b77c7dfeb734519a50a28be49024727

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765746B2