Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-Chloro-3-[(2-Cyanopropan-2-Yl)oxy]-N-{5-[{2-[(Cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-B]pyridin-5-Yl}(Methyl)amino]-2-Fluorophenyl}benzamide

To a solution of 2-chloro-3-(1-cyano-1-methylethoxy)benzoic acid (4.8 g, 20 mmol) produced in Example C70(iii) in pyridine (100 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (7.6 g, 20 mmol), and the mixture was stirred at room temperature for 2 hr. To the obtained solution was added N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (3.57 g, 9.99 mmol), and the mixture was stirred at 90° C. for 3 hr. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (350 mL), and washed with water (350 mL). The aqueous layer was extracted with ethyl acetate (150 mL). The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (250 mL×2) and saturated brine (250 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=60/40→20/80), the obtained solution was concentrated under reduced pressure, and the residue was crystallized from ethyl acetate to give the title compound (5.02 g, 87%) as a colorless powder.

1. stirringthe mixture was stirred at 90° C. for 3 hr
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationconcentrated under reduced pressure
4. additionThe obtained residue was diluted with ethyl acetate (350 mL)
5. washwashed with water (350 mL)
6. extractionThe aqueous layer was extracted with ethyl acetate (150 mL)
7. washThe combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (250 mL×2) and saturated brine (250 mL)
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationThe insoluble material was filtered off
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=60/40→20/80)
12. concentrationthe obtained solution was concentrated under reduced pressure
13. customthe residue was crystallized from ethyl acetate

ORDレコード

ord-b56c95b3f139490f872cafc41163458a

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08344135B2