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Potassium Phosphate, Tribasic → 2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[1-methyl-5-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde

HRID 593032
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 593032
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:19][CH2:18][N:17]3[C:10](=[CH:11][C:12]4[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15][C:16]=43)[C:9]2=[O:22])[C:3]=1[CH:23]=[O:24].[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([C:48]([N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[O:49])=[CH:44][N:43]=2)[C:27]1=[O:56].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>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(#N)C>[CH3:20][C:14]1([CH3:21])[CH2:13][C:12]2[CH:11]=[C:10]3[N:17]([CH2:18][CH2:19][N:8]([C:4]4[C:3]([CH:23]=[O:24])=[C:2]([C:30]5[CH:29]=[C:28]([NH:41][C:42]6[CH:47]=[CH:46][C:45]([C:48]([N:50]7[CH2:55][CH2:54][O:53][CH2:52][CH2:51]7)=[O:49])=[CH:44][N:43]=6)[C:27](=[O:56])[N:26]([CH3:25])[CH:31]=5)[CH:7]=[CH:6][N:5]=4)[C:9]3=[O:22])[C:16]=2[CH2:15]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-oneHCID 768540784-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehyde

Produkt 1

HCID 86684509
2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[1-methyl-5-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde
Ausbeute 83,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterKatalysatorHCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (100 mg, 0.29 mmol), 1-methyl-3-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-di-oxaborolan-2-yl)pyridin-2(1H)-one 111c (192 mg, 0.44 mmol), Pd(dppf)Cl2 (12 mg, 0.015 mmol), K3PO4 (123 mg, 0.58 mmol), sodium acetate (47 mg, 0.58 mmol), acetonitrile (10 mL), and water (5 drops). After three cycles of vacuum/N2 flush, the mixture was heated at 100° C. for 1 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. It was cooled to room temperature, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography (dichloromethane/methanol 40:1) to afford 269a (150 mg, 83%) as a brown solid. MS-ESI: [M+H]+ 621.8

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/N2 flush
  3. temperatureIt was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica-gel column chromatography (dichloromethane/methanol 40:1)

Quellen und Nachweise

ORD-Eintrag
ord-c3c1172441154295a8160c47c2e0749f
Quelldatensatz
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09238655B2

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