Water → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-{4-[(methylsulfonyl)amino]phenyl}-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 475994Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 475994
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[CH3:27][S:28]([NH:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)(=[O:30])=[O:29].C(=O)(O)[O-].[Na+].O>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:35]2[CH:34]=[CH:33][C:32]([NH:31][S:28]([CH3:27])(=[O:29])=[O:30])=[CH:37][CH:36]=2)[CH:3]=1)=[O:15]

Komponenten

7

Edukt 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2773537(4-Methanesulfonamidophenyl)boronic acidHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Produkt 1

HCID 56598146N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-{4-[(methylsulfonyl)amino]phenyl}-1H-pyrazolo[3,4-b]pyridine-4-carboxamideAusbeute 37,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Versuchsvorschrift

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (75 mg, 0.2 mmol) and {4-[(methylsulfonyl)amino]phenyl}boronic acid (43.1 mg, 0.2 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.2 mg, 0.01 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (50.6 mg, 0.6 mmol) was added, the vessel was sealed, and the reaction mixture was irradiated (microwave) at 150° C. for 25 min. After cooling, 2 mL of water was added to the black mixture and solids that precipitated were filtered. DCM/MeOH (1:1) was added, the mixture was pre-absorbed on silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was suspended in EtOAc heated, and sonicated. Some hexanes was added and the contents allowed to cool to room temperature. Solids that precipitated were filtered. The solid was then suspended in EtOH, heated, and sonicated. After cooling to room temperature, the solids were filtered and dried to afford the title compound (38 mg, 36%) as a beige solid. LCMS E-S (M+H)=509.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (s, 1H), 10.05 (br. s., 1H), 8.93 (t, J=4.93 Hz, 1H), 8.35 (s, 1H), 8.24 (m, J=8.59 Hz, 2H), 8.11 (s, 1H), 7.37 (m, J=8.84 Hz, 2H), 5.91 (s, 1H), 5.32 (quin, J=6.69 Hz, 1H), 4.41 (d, J=4.80 Hz, 2H), 3.08 (s, 3H), 2.23 (s, 3H), 2.13 (s, 3H), 1.55 (s, 3H), 1.54 (s, 3H).

Aufarbeitung

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customthe vessel was sealed
  4. customthe reaction mixture was irradiated (microwave) at 150° C. for 25 min
  5. temperatureAfter cooling
  6. customthat precipitated
  7. filtrationwere filtered
  8. additionDCM/MeOH (1:1) was added
  9. customthe mixture was pre-absorbed on silica gel
  10. custompurified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  11. temperatureheated
  12. customsonicated
  13. additionSome hexanes was added
  14. customSolids that precipitated
  15. filtrationwere filtered
  16. temperatureheated
  17. customsonicated
  18. temperatureAfter cooling to room temperature
  19. filtrationthe solids were filtered
  20. customdried

Quellen und Nachweise

ORD-Eintrag
ord-481b63fe417449bfa7daeae4fc34cbf0
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637509B2

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