Acetonitrile → HCID 178489396, compound

Into a 5 mL Personal Chemistry microwave reaction vial were added 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (0.0498 g, 0.103 mmol), (2-Amino-5-bromo-phenyl)-morpholin-4-yl-methanone (0.0378 g, 0.132 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (13.4 mg, 0.017 mmol), acetonitrile (1 mL) and saturated aqueous NaHCO3 (1 mL). The vial was sealed, purged with N2, and irradiated in a Personal Chemistry Optimizer at 90° C. for 5 min. The layers were separated, and the aqueous phase was extracted 3× with EtOAc. The combined organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in 5 mL of a solution consisting of 1 part HClO4 (70%, ACS) and 20 parts glacial acetic acid, and the solution was stirred at rt for 8 h. The reaction mixture was concentrated under vacuum, and neutralized to pH 7 with saturated NaHCO3 followed by solid NaHCO3. The quenched reaction mixture was partitioned between EtOAc and water, the layers were separated, and the aqueous phase was extracted 2× with EtOAc. The combined organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. Purification by mass-triggered LC (positive mode, ESI) through a C-18 reverse-phase column (Thomson Instrument Co. ODS-A 100 A, 5μ, 50×21.3 mm, eluting at 20 mL/min with acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid) in a 5-95% gradient afforded the title compound, which upon lysophilization appeared as a brown viscous oil (12.9 mg, 29%). 1H-NMR (500 MHz, d6-DMSO) δ 13.71 (br. s, 1H), 8.74 (d, J=2.0 Hz, 1H), 8.16 (d, J=2.0 Hz, 1H), 7.62 (d, J=7.5 Hz, 1H), 7.49 (dd, J=2.5, 8.0 Hz, 1H), 7.45 (m, 1H), 7.37 (d, J=2.0 Hz, 1H), 7.20 (d, J=8.0 Hz, 1H), 7.08 (t, J=8.5 Hz, 1H), 6.81 (d, J=8.0 Hz, 1H), 5.37 (s, 2H), 3.83 (s, 3H), 3.60 (m, 4H), 3.49 (m, 4H); MS: m/z 430.1 [MH+].

1. customInto a 5 mL Personal Chemistry microwave reaction
2. customThe vial was sealed
3. custompurged with N2
4. customirradiated in a Personal Chemistry Optimizer at 90° C. for 5 min
5. customThe layers were separated
6. extractionthe aqueous phase was extracted 3× with EtOAc
7. additionThe combined organic phase was treated with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe crude product was dissolved in 5 mL of a solution
12. concentrationThe reaction mixture was concentrated under vacuum
13. customThe quenched reaction mixture
14. customwas partitioned between EtOAc and water
15. customthe layers were separated
16. extractionthe aqueous phase was extracted 2× with EtOAc
17. additionThe combined organic phase was treated with brine
18. dry with materialdried (Na2SO4)
19. filtrationfiltered
20. concentrationconcentrated
21. customPurification by mass-triggered LC (positive mode, ESI) through a C-18 reverse-phase column (Thomson Instrument Co
22. washODS-A 100 A, 5μ, 50×21.3 mm, eluting at 20 mL/min with acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid) in a 5-95% gradient

ORD record

ord-d197d055fd664ead9d0b1de593106d1d

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268994B2