Methanol → N-(2,4-dimethoxybenzyl)thiazol-2-amine

2,4 Dimethoxybenzaldehyde (25 g, 150 mmol, 1 eq), 2 aminothiazole (15.1 g, 150 mmol, 1 eq) and piperidine (150 mg, 1.76 mmol, 0.012 eq) were combined in dichloroethane (500 ml) and the reaction mixture heated to reflux over sieves for 18 hours. The sieves were removed by filtration and the reaction mixture diluted with MeOH (300 ml). Sodium borohydride (25 g, 662 mmol, 4.4 eq) was added portionwise and the reaction mixture heated to reflux for 2 hours. The mixture was cooled, quenched with water and the organic solvent evaporated in vacuo. The reaction mixture was extracted into ethyl acetate and the combined organic solutions extracted with 2M HCl. The acidic solution was basified with potassium carbonate, re-extracted into ethyl acetate, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was purified by column chromatography eluting with 9:1 DCM:MeOH to yield the title compound (24 g, 96 mmol, 64%).

1. temperaturethe reaction mixture heated
2. temperatureto reflux over sieves for 18 hours
3. customThe sieves were removed by filtration
4. additionthe reaction mixture diluted with MeOH (300 ml)
5. temperaturethe reaction mixture heated
6. temperatureto reflux for 2 hours
7. temperatureThe mixture was cooled
8. customquenched with water
9. customthe organic solvent evaporated in vacuo
10. extractionThe reaction mixture was extracted into ethyl acetate
11. extractionthe combined organic solutions extracted with 2M HCl
12. extractionre-extracted into ethyl acetate
13. dry with materialdried over sodium sulphate
14. filtrationfiltered
15. customevaporated in vacuo
16. customThe crude material was purified by column chromatography
17. washeluting with 9:1 DCM

ORD record

ord-39b4b9de613e4555a9d2149f29dcf0ba

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08357711B2