Potassium Phosphate, Tribasic → 4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl-amino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehyde

HRID 592960Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592960
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[CH2:21][C:20]3[N:19]4[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]4)=[CH:13][C:12]=3[C:11]2=[O:22])[N:5]=[CH:4][CH:3]=1.[CH3:23][N:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[C:26]([NH:39][C:40]2[CH:45]=[CH:44][C:43]([N:46]3[CH2:51][CH2:50][N:49]([CH:52]4[CH2:55][O:54][CH2:53]4)[CH2:48][C@@H:47]3[CH3:56])=[CH:42][N:41]=2)[C:25]1=[O:57].C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].O.C(#N)C>[CH3:23][N:24]1[C:25](=[O:57])[C:26]([NH:39][C:40]2[CH:45]=[CH:44][C:43]([N:46]3[CH2:51][CH2:50][N:49]([CH:52]4[CH2:53][O:54][CH2:55]4)[CH2:48][CH:47]3[CH3:56])=[CH:42][N:41]=2)=[CH:27][C:28]([C:2]2[C:7]([CH:8]=[O:9])=[C:6]([N:10]3[CH2:21][C:20]4[N:19]5[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]5)=[CH:13][C:12]=4[C:11]3=[O:22])[N:5]=[CH:4][CH:3]=2)=[CH:29]1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866837011-methyl-3-((5-((2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-oneHCID 866844524-Chloro-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehyde

Produkt 1

HCID 866844534-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl-amino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehydeAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 238e (150 mg, 0.48 mmol, 1.0 eq.), (S)-1-methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 191j (459 mg, 0.95 mmol, 2.0 eq.), Pd(dppf)Cl2 (39 mg, 0.048 mmol, 0.1 eq.), sodium acetate (78 mg, 0.95 mmol, 2.0 eq.), K3PO4 (202 mg, 0.95 mmol, 2.0 eq.), acetonitrile (10 mL), and water (1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 85° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/ethanol to afford 238f (90 mg, 30%) as a yellow solid. MS-ESI: [M+H]+ 635.3.

Aufarbeitung

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 40:1 dichloromethane/ethanol

Quellen und Nachweise

ORD-Eintrag
ord-baaaab8531854a38a7811708f4524547
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238655B2

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