Chloroiodomethane → HCID 57586427, compound

Temperature

-78 °C

A 500 mL round-bottomed flask was charged with methyl 6-methylnicotinate (3.0 g, 20 mmol), chloroiodomethane (7.1 ml, 97 mmol), and 50 mL of THF. After cooling to −78° C., a freshly prepared solution of LDA (1M in THF made from diisopropylamine (14 ml, 99 mmol) and BuLi (39 ml, 97 mmol)) was added drop-wise over 1.5 h. After that time, the reaction was quenched with a solution of 5 mL HOAc in 15 mL of THF. The mixture was warmed to rt and diluted with sat. aq. NaHCO3. The mixture was concentrated then portioned between EtOAc and water. The organic layer was separated, dried over MgSO4, filtered, and concentrated to give a brown oil. To this oil was added thiourea (1.5 g, 20 mmol), NaOAc (4.9 g, 60 mmol) and 30 mL of EtOH. The mixture was heated at 80° C. for 15 min then cooled to rt. The mixture was concentrated in vacuo then diluted with water and EtOAc. The layers were separated and the organics were dried (MgSO4), filtered and concentrated to give an oil. Purification by MPLC (80 g, 10-100% EA/Hex) gave 4-(6-methylpyridin-3-yl)thiazol-2-amine as a yellow solid.

1. customAfter that time, the reaction was quenched with a solution of 5 mL HOAc in 15 mL of THF
2. temperatureThe mixture was warmed to rt
3. additiondiluted with sat. aq. NaHCO3
4. concentrationThe mixture was concentrated
5. customThe organic layer was separated
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto give a brown oil
10. temperatureThe mixture was heated at 80° C. for 15 min
11. temperaturethen cooled to rt
12. concentrationThe mixture was concentrated in vacuo
13. additionthen diluted with water and EtOAc
14. customThe layers were separated
15. dry with materialthe organics were dried (MgSO4)
16. filtrationfiltered
17. concentrationconcentrated
18. customto give an oil
19. customPurification by MPLC (80 g, 10-100% EA/Hex)

ORD record

ord-e630f4479ad74fb49733415a7719e037

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324396B2