Potassium Phosphate, Tribasic → (4-(1-Methyl-5-(5-(3-(oxetan-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 592695Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592695
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:22]4[CH2:23][CH2:24][CH:18]3[CH2:19][N:20]([CH:25]3[CH2:28][O:27][CH2:26]3)[CH2:21]4)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:29]([O:32][CH2:33][C:34]1[C:35]([N:43]2[CH2:55][CH2:54][N:46]3[C:47]4[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=4[CH:53]=[C:45]3[C:44]2=[O:56])=[N:36][CH:37]=[CH:38][C:39]=1B(O)O)(=[O:31])[CH3:30].[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>[C:29]([O:32][CH2:33][C:34]1[C:35]([N:43]2[CH2:55][CH2:54][N:46]3[C:47]4[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=4[CH:53]=[C:45]3[C:44]2=[O:56])=[N:36][CH:37]=[CH:38][C:39]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:22]4[CH2:23][CH2:24][CH:18]3[CH2:19][N:20]([CH:25]3[CH2:28][O:27][CH2:26]3)[CH2:21]4)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:31])[CH3:30]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866842695-Bromo-1-methyl-3-(5-(3-(oxetan-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-ylamino)pyridine-2(1H)-oneHCID 866842713-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid

Produkt 1

HCID 86684270(4-(1-Methyl-5-(5-(3-(oxetan-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl AcetateAusbeute 42,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 152e (300 mg, 0.67 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113h (257 mg, 0.67 mmol), Pd(dppf)Cl2 (55 mg, 0.067 mmol), K3PO4 (284 mg, 1.34 mmol), sodium acetate (110 mg, 1.34 mmol), water (6 drops), and acetonitrile (20 mL). After three cycles of vacuum/argon flush, the mixture was stirred at reflux for 3 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 30:1 dichloromethane/methanol to afford 152f as a brown solid (200 mg, 42%). MS-ESI: [M+H]+ 705.4.

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. temperatureat reflux for 3 h
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 30:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-b6ea28f6e97345e0b23df0eab1af4864
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238655B2

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