Cyanamide → [4-Amino-2-[4-(2-dimethylaminoethoxy)-phenylamino]-thiazol-5-yl]-(3-methoxy-phenyl)-methanone

To a stirred mixture of [2-(4-isothiocyanato-phenoxy)-ethyl]-dimethylamine (0.6 g, 2.7 mmol) (from Step A) and cyanamide (0.123 g, 2.95 mmol) in acetonitrile (10 mL) and tert-butanol (10 mL), a solution of potassium tert-butoxide (2.7 mL, 1.0 M in tert-BuOH) was added. After 30 minutes at room temperature, 2-bromo-3′-methoxyacetophenone was added. The reaction mixture was stirred at room temperature for 1 hour and then refluxed for 1 hour. The chilled reaction mixture was diluted with ether and excess anhydrous hydrochloric acid/ether solution was added. The solids were filtered, washed with ether and then dissolved in dichloromethane/aqueous sodium bicarbonate. The dried (Na2SO4) organic solution was diluted with toluene (25 mL), concentrated, and refluxed to remove dichloromethane, The cooled mixture was diluted with hexane and filtered to give 0.47 g (42%) of [4-amino-2-[4-(2-dimethylaminoethoxy)-phenylamino]-thiazol-5-yl]-(3-methoxy-phenyl)-methanone as a yellow solid, mp 130° C. (dec). Mass spectrum (ES) MH+=413.

1. temperaturerefluxed for 1 hour
2. customThe chilled reaction mixture
3. additionwas added
4. filtrationThe solids were filtered
5. washwashed with ether
6. dissolutiondissolved in dichloromethane/aqueous sodium bicarbonate
7. dry with materialThe dried (Na2SO4) organic solution
8. additionwas diluted with toluene (25 mL)
9. concentrationconcentrated
10. temperaturerefluxed
11. customto remove dichloromethane
12. additionThe cooled mixture was diluted with hexane
13. filtrationfiltered

ORD record

ord-aa9db080915744bb9a8fdb830efbbac9

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06818663B2