Lithium Hexamethyldisilazide → 4-(2,3-Dichlorobenzyl)-2-(methylthio)thiazolo[4,5-d]pyrimidin-7(4H)-one

Temperature

2.5 °C

To a suspension of 2-(methylthio)thiazolo[4,5-d]pyrimidin-7(4H)-one (2.978 g, 14.94 mmol) in THF (200 mL) at 0° C. was added dropwise of LiHMDS (18.3 mL, 16.44 mmol). The resulting mixture was stirred at 0-5° C. for 3 hours and 1-(bromomethyl)-2,3-dichlorobenzene (3.946 g, 16.44 mmol) in THF (30 mL) was added dropwise to the reaction mixture over a period of 2 hours. The reaction mixture was allowed to warm to ambient temperature slowly and stirred at ambient temperature for 16 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (2×20 cm, DCM:MeOH=30:1 elution) to give the desired product as a white solid (0.671 g, 13%). 1H NMR (300 MHz, CDCl3) δ 8.33 (s, 1H), 7.50 (m, 1H), 7.26˜7.16 (m, 2H), 5.56 (s, 2H), 2.74 (s, 3H); LC-MS: 358 (MH+); IR (thin film): 3073, 2986, 1651, 1619, 1598, 1426, 1384, 1221, 1055 cm−1.

1. temperatureto warm to ambient temperature slowly
2. stirringstirred at ambient temperature for 16 hours
3. filtrationThe reaction mixture was filtered
4. concentrationthe filtrate was concentrated under reduced pressure
5. customThe residue was purified by flash column chromatography on silica gel (2×20 cm, DCM:MeOH=30:1 elution)

ORD record

ord-b30eac4a4e5b4056b414727976b541ad

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410095B2