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Acetonitrile → HCID 178489396, Verbindung

HRID 272035
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 272035
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11](COCC[Si](C)(C)C)C=1.[NH2:35][C:36]1[CH:41]=[CH:40][C:39](Br)=[CH:38][C:37]=1[C:43]([N:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1)=[O:44].C([O-])(O)=O.[Na+].C(#[N:58])C>>[NH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:58][NH:11][C:12]3=[N:13][CH:14]=2)=[CH:38][C:37]=1[C:43]([N:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1)=[O:44]
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Komponenten

5

Edukt 4

HCID 6342AcetonitrileHCID 516892Sodium BicarbonateHCID 44448998(2-Amino-5-bromophenyl)(morpholino)methanoneHCID 598248843-(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

Produkt 1

HCID 178489396HCID 178489396, Verbindung

Versuchsvorschrift

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 100A, 5 μ, 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) δ13.71 (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, 4 H), 3.49 (m, 4 H);

Aufarbeitung

  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 100A, 5 μ, 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

Quellen und Nachweise

ORD-Eintrag
ord-0a4c251720464f3cb8a0a06223deed4b
Quelldatensatz
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07452993B2

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