1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N'-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-[(2R) 1,4-dioxan-2-ylmethyl]-N-methylsulfamide

Temperature

60 °C

A stirred solution of 7-bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (10 g, 1.0 equiv), {[((2R)1,4-dioxan-2-ylmethyl)(methyl)amino]-sulfonyl}amine (6.9 g, 1.05 equiv), sodium tert-butoxide (6.6 g, 2.2 equiv), Pd2(dba)3 (0.29 g, 0.01 equiv), and Xantphos (0.36 g, 0.02 equiv) in toluene (250 mL) was thoroughly de-gassed, and then put under a nitrogen atmosphere. The resulting reaction mixture was then heated to 60° C., and left to age at this temperature until the reaction was complete (typically 1.5 h). The batch was then cooled to ambient temperature, and water (150 mL) was added. The resulting biphasic mixture was allowed to settle, and the aqueous layer was collected. The organic layer was extracted with 0.2 M aqueous NaOH (150 mL), the aqueous layers were combined and then washed twice with DCM (100 mL, then 50 mL). To the resulting aqueous layer was added DCM (200 mL) followed by concentrated hydrochloric acid (˜10 mL). After mixing thoroughly, the two layers were separated and the aqueous layer was extracted twice with DCM (100 mL, then 50 mL). The combined DCM layers were washed with water (100 mL), and then solvent-switched into toluene (to a final volume of ˜150 mL). The resulting slurry was aged at ˜20° C. for at least 1 h and then filtered, washing the filter-cake with toluene (30 mL, then 20 mL). The resulting solid was dried under vacuum at 40° C. to afford the title compound.

1. customThe resulting reaction mixture
2. waitleft to age at this temperature until the reaction
3. customtypically 1.5 h
4. temperatureThe batch was then cooled to ambient temperature
5. customthe aqueous layer was collected
6. extractionThe organic layer was extracted with 0.2 M aqueous NaOH (150 mL)
7. washwashed twice with DCM (100 mL
8. additionTo the resulting aqueous layer was added DCM (200 mL)
9. additionAfter mixing thoroughly
10. customthe two layers were separated
11. extractionthe aqueous layer was extracted twice with DCM (100 mL
12. washThe combined DCM layers were washed with water (100 mL)
13. waitThe resulting slurry was aged at ˜20° C. for at least 1 h
14. filtrationfiltered
15. washwashing the
16. filtrationfilter-cake with toluene (30 mL
17. customThe resulting solid was dried under vacuum at 40° C.

ORD record

ord-bac98a1442494b9f9db7395396cf6b3a

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893081B2