Dimethylformamide → HCID 44124592, compound

Temperature

150 °C

One equivalent of 6-bromo-2-chlorobenzo[d]thiazole (248 mg, 1.0 mmol) and 1.1 equivalents of 4-(pyrrolidin-1-yl)piperidine (0.170 g, 1.1 mmol) were weighed into a 10 mL CEM microwave vial equipped with a magnetic stirbar. N,N-Dimethylformamide (1.0 mL) and three equivalents of N,N-diisopropylethylamine (0.524 ml, 3.00 mmol) were added via syringe. The reaction mixture was heated to 150° C. under microwave irradiation with the cooling power on for 15 minutes. The reaction mixture was transferred to a 250 mL round bottom flask (methanol rinse) and volatiles were removed under reduced pressure. The residue was partitioned between saturated aqueous sodium carbonate and CHCl3. The aqueous layer was extracted once more with CHCl3, then the combined organic extracts were washed with brine, dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure to give a solid. This crude solid was purified by column chromatography on an Analogix IF-280 (Analogix SF15-12 g, 100% dichloromethane to 97:3 dichloromethane/2 M ammonia in methanol). Fractions containing product were combined and concentrated under reduced pressure to give a solid that was dissolved in hot ethyl acetate, dried (MgSO4), and filtered. The filtrate was placed in a 0° C. freezer to promote crystallization. Crystals were collected by filtration and dried in a vacuum oven to give 6-bromo-2-(4-(pyrrolidin-1-yl)piperidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.51-1.66 (m, 2H), 1.78-1.88 (m, 4H), 2.04-2.14 (m, 2H), 2.34-2.46 (m, 1H), 2.63-2.72 (m, 4H), 3.16-3.27 (m, 2H), 4.06-4.15 (m, 2H), 7.33 (d, J=9 Hz, 1H), 7.39 (dd, J=2, 9 Hz, 1H), 7.79 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 366 (M+H)+.

1. customvial equipped with a magnetic stirbar
2. customThe reaction mixture was transferred to a 250 mL round bottom flask
3. wash(methanol rinse) and volatiles
4. customwere removed under reduced pressure
5. customThe residue was partitioned between saturated aqueous sodium carbonate and CHCl3
6. extractionThe aqueous layer was extracted once more with CHCl3
7. washthe combined organic extracts were washed with brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customto give a solid
12. customThis crude solid was purified by column chromatography on an Analogix IF-280 (Analogix SF15-12 g, 100% dichloromethane to 97:3 dichloromethane/2 M ammonia in methanol)
13. additionFractions containing product
14. concentrationconcentrated under reduced pressure
15. customto give a solid
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. customwas placed in a 0° C.
19. customcrystallization
20. filtrationCrystals were collected by filtration
21. customdried in a vacuum oven

ORD record

ord-3939131741ea40648b9d4c72fda185e1

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580968B2