HCID 58513750, compound → HCID 54673608, compound

A solution of 4,5-dichloro-2-(4-(pyrrolidin-1-ylmethyl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (198 mg, 0.396 mmol) (Example 128B), 1-(5-(tributylstannyl)pyridin-2-yl)cyclobutanol (Example 143A) (260 mg, 0.593 mmol), and bis(triphenylphosphine)palladium dichloride (19.43 mg, 0.028 mmol) in N,N-dimethylformamide (1.318 mL) was heated to 100° C. for 16 hours. The reaction was cooled to room temperature and quenched by the addition of an aqueous potassium fluoride solution (3 g potassium fluoride in 6 mL water) and ethyl acetate (10 mL). The mixture was stirred vigorously for 16 hours and filtered through diatomaceous earth, eluting with ethyl acetate. The eluent was washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in a solvent mixture of 2 N aqueous sodium hydroxide solution (1.0 mL) and methanol (3 mL). The solution was heated to 105° C. by microwave irradiation (Biotage, Initiator) for 5 minutes. The reaction was cooled to room temperature and diluted with dimethyl sulfoxide (1 mL). The resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 m column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.50 (bs, 1H), 8.77 (dd, J=2.3, 0.8 Hz, 1H), 8.34 (s, 1H), 8.02 (dd, J=8.1, 2.3 Hz, 1H), 7.94-7.86 (m, 2H), 7.78 (dd, J=8.1, 0.8 Hz, 1H), 7.40-7.33 (m, 2H), 6.72 (s, 1H), 5.86 (s, 1H), 3.59 (s, 2H), 2.74-2.61 (m, 2H), 2.46-2.39 (m, 4H), 2.35-2.22 (m, 2H), 2.05-1.82 (m, 2H), 1.78-1.61 (m, 4H); MS ESI(+) m/z 459.2 [M+H]+.

1. customquenched by the addition of an aqueous potassium fluoride solution (3 g potassium fluoride in 6 mL water) and ethyl acetate (10 mL)
2. filtrationfiltered through diatomaceous earth
3. washeluting with ethyl acetate
4. washThe eluent was washed with aqueous saturated sodium bicarbonate solution
5. dry with materialdried with anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe residue was dissolved in a solvent mixture of 2 N aqueous sodium hydroxide solution (1.0 mL) and methanol (3 mL)
9. temperatureThe solution was heated to 105° C. by microwave irradiation (Biotage, Initiator) for 5 minutes
10. temperatureThe reaction was cooled to room temperature
11. additiondiluted with dimethyl sulfoxide (1 mL)
12. customThe resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 m column
13. washeluting with a gradient of 5% B in A to 75% B in A over 25 minutes

ORD record

ord-4bfa035987ee4431a83dcddaddb341e0

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691810B2