Aniline → HCID 44223338, compound

A round bottom flask equipped with a stir bar and nitrogen inlet was charged with aniline (4.2 mg, 0.046 mmol) and dry toluene (0.5 mL) under a nitrogen atmosphere. Trimethyl aluminum (8.0 μL, 0.160 mmol, 7 eq.) was added to this solution, and this mixture was stirred at room temperature for 20 minutes. Methyl 5-(2,6-difluoro-3-(propylsulfonamido)benzamido)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (13.5 mg, 0.023 mmol, see Example 14) was added in one portion, and the reaction mixture warmed to 90° C. for 30 minutes. The reaction mixture was then allowed to cool to room temperature. The mixture was then quenched carefully with 30% aqueous sodium potassium tartrate and extracted with ethyl acetate (2×). The extracts were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in THF (1 mL), and a 1M aqueous LiOH solution (1 mL) was then added. The mixture was stirred at room temperature for 16 hours, diluted with AcOH/water and extracted with EtOAc (2×). The extracts were washed with saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated. The resulting residue was subjected to preparative TLC purification (2×0.5 mm plates, 10% MeOH/DCM) to afford 5-(2,6-difluoro-3-(propylsulfonamido)benzamido)-N-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide (4.2 mg, 36%). 1H NMR (400 MHz, DMSO-d6) δ 12.31 (s, 1H), 10.97 (s, 1H), 9.76-9.87 (m 2H), 8.89-8.96 (m, 1H), 8.42-8.55 (m 2H), 7.73-7.80 (m, 2H), 7.51-7.59 (m, 1H), 7.20-7.38 (m, 3H), 7.03-7.11 (m, 1H), 3.06-3.14 (m, 2H), 1.71-1.82 (m, 2H), 0.94-1.04 (m, 3H); m/z (APCI-neg) M−1=512.1; (APCI-pos) M+1=514.0.

1. customA round bottom flask equipped with a stir bar and nitrogen inlet
2. temperaturethe reaction mixture warmed to 90° C. for 30 minutes
3. temperatureto cool to room temperature
4. customThe mixture was then quenched carefully with 30% aqueous sodium potassium tartrate
5. extractionextracted with ethyl acetate (2×)
6. dry with materialThe extracts were dried over sodium sulfate
7. concentrationconcentrated under reduced pressure
8. dissolutionThe resulting residue was dissolved in THF (1 mL)
9. additiona 1M aqueous LiOH solution (1 mL) was then added
10. stirringThe mixture was stirred at room temperature for 16 hours
11. additiondiluted with AcOH/water
12. extractionextracted with EtOAc (2×)
13. washThe extracts were washed with saturated sodium bicarbonate solution
14. dry with materialdried over sodium sulfate
15. concentrationconcentrated
16. customThe resulting residue was subjected to preparative TLC purification (2×0.5 mm plates, 10% MeOH/DCM)

ORD record

ord-c0aec2abec4d443a9406101cad44e991

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08338452B2