Benzyl mercaptan → HCID 86687445, compound

A two-neck round-bottom flask was charged with 6-bromo-1-chlorophthalazine (Pharmablock, Nanjing Hi-Tech Zone, China, 4.44 g, 18.24 mmol), Xantphos (0.528 g, 0.912 mmol), and Pd2(dba)3 (0.417 g, 0.456 mmol). 1,4-dioxane (36.5 ml) and N,N-diisopropylethylamine (6.37 ml, 36.5 mmol) were added. The flask was fitted with a reflux condenser and placed in an 80° C. heating bath. After 5 min, benzyl mercaptan (2.265 ml, 19.15 mmol) was added drop wise. After 20 min. the mixture was cooled, then concentrated under a vacuum. EtOAc (about 25 mL) was added to the residue, and the flask was rotated on the rotovap in a 40° C. bath for 1.5 h. This removed most of the solid from the sides of the flask. The flask was sonicated for 30 s, then the mixture was concentrated under a vacuum. The residue was taken up in EtOAc to form a thick slurry. The flask was sonicated for 30 s, then the mixture was filtered. The collected solid was washed with several large volumes of EtOAc (until the filtrates were essentially colorless). The filtrate was concentrated, and the residue was purified by chromatography on silica gel (80-g column with a 25-g silica gel loading column, 0 to 50% EtOAc/Heptane, then 50 to 100% EtOAc/Heptane). The resulting solid was taken up in heptane, sonicated for 30 s, then filtered. The collected solid was washed with heptane (3×, which removed some of the yellow color), and dried under a stream of N2 (g) for 20 min to give 6-(benzylthio)-1-chlorophthalazine (3.975 g, 13.86 mmol, 76% yield) as a light-orange powder: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=9.28 (d, J=0.7 Hz, 1H), 8.14 (d, J=8.8 Hz, 1H), 7.82 (dd, J=1.9, 8.8 Hz, 1H), 7.69 (d, J=1.8 Hz, 1H), 7.45-7.28 (m, 5H), 4.35 (s, 2H); m/z (ESI) 287.2 (M+H)+.

1. customThe flask was fitted with a reflux condenser
2. customplaced in an 80° C.
3. temperatureheating bath
4. temperatureAfter 20 min. the mixture was cooled
5. concentrationconcentrated under a vacuum
6. additionEtOAc (about 25 mL) was added to the residue
7. customwas rotated on the rotovap in a 40° C.
8. customfor 1.5 h
9. customThis removed most of the solid from the sides of the flask
10. customThe flask was sonicated for 30 s
11. concentrationthe mixture was concentrated under a vacuum
12. customto form a thick slurry
13. customThe flask was sonicated for 30 s
14. filtrationthe mixture was filtered
15. washThe collected solid was washed with several large volumes of EtOAc (until the filtrates
16. concentrationThe filtrate was concentrated
17. customthe residue was purified by chromatography on silica gel (80-g column with a 25-g silica gel loading column, 0 to 50% EtOAc/Heptane
18. customsonicated for 30 s
19. filtrationfiltered
20. washThe collected solid was washed with heptane (3×, which
21. customremoved some of the yellow color), and
22. dry with materialdried under a stream of N2 (g) for 20 min

ORD record

ord-9ab8218529a34d27a0514883e89e5a6c

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012443B2