Pyridine → 1,1-Dimethylethyl 3-{[(5-chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazole-1-carboxylate

To a solution of 1,1-dimethylethyl 3-amino-4-(methyloxy)-1H-indazole-1-carboxylate (for a preparation see Intermediate 5) (6.03 g, 22.9 mmol) and 5-chloro-2-thiophenesulfonyl chloride (3.07 mL, 22.9 mmol) in DCM (30 mL) was added dropwise at 0° C. a solution of pyridine (3.7 mL, 46 mmol) in DCM. The reaction mixture was stirred allowing to warm from 0° C. to room temperature over 2 h, then stirred at room temperature over the weekend. Pyridine (50 mL) were added and resulting mixture was stirred at 50° C. for another 24 h. The reaction mixture was then quenched with 50 mL of a saturated NaHCO3 solution. The organic layer was partitioned and the aqueous layer was further extracted with 50 mL of DCM. The organic solutions were combined, washed with water (50 mL) then brine (50 mL), and dried with an hydrophobic frit. The crude product was purified by chromatography on two 100 g Si cartridges on Flashmaster, eluting with 0 to 25% gradient of EtOAc in DCM, over 60 min to give the desired product as a pale orange solid: (2.21 g, 22%). LCMS (System A) RT=1.35 min, ES+ve m/z 444 (M+H)+.

1. temperatureto warm from 0° C. to room temperature over 2 h
2. stirringstirred at room temperature over the weekend
3. customresulting mixture
4. stirringwas stirred at 50° C. for another 24 h
5. customThe reaction mixture was then quenched with 50 mL of a saturated NaHCO3 solution
6. customThe organic layer was partitioned
7. extractionthe aqueous layer was further extracted with 50 mL of DCM
8. washwashed with water (50 mL)
9. dry with materialbrine (50 mL), and dried with an hydrophobic frit
10. customThe crude product was purified by chromatography on two 100 g Si cartridges on Flashmaster
11. washeluting with 0 to 25% gradient of EtOAc in DCM, over 60 min

ORD record

ord-c72c7c34e99d40bd960503b6c4f5d6a3

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304446B2