Potassium Phosphate, Tribasic → (4-(1-Ethyl-5-(5-(1-methylpiperidin-4-yl)pyridin-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 592946Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592946
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[CH2:56][CH2:55][N:47]3[C:48]4[CH2:49][CH2:50][CH2:51][CH2:52][C:53]=4[CH:54]=[C:46]3[C:45]2=[O:57])=[N:31][CH:32]=[CH:33][C:34]=1B1OC(C)(C)C(C)(C)O1)(=[O:26])[CH3:25].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.O.O.[C:69]([O-])(=O)C.[Na+]>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.O>[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[CH2:56][CH2:55][N:47]3[C:48]4[CH2:49][CH2:50][CH2:51][CH2:52][C:53]=4[CH:54]=[C:46]3[C:45]2=[O:57])=[N:31][CH:32]=[CH:33][C:34]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH2:8][CH3:69])[CH:7]=1)(=[O:26])[CH3:25]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 23665404Sodium Acetate TrihydrateHCID 580436455-Bromo-1-methyl-3-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridin-2(1H)-oneHCID 86684143(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Produkt 1

HCID 86684438(4-(1-Ethyl-5-(5-(1-methylpiperidin-4-yl)pyridin-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 69,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A round-bottomed flask equipped with a reflux condenser was charged with 232d (160 mg, 0.40 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113i (191 mg, 0.50 mmol), Pd(dppf)Cl2 (20 mg, 0.024 mmol), K3PO4 (180 mg, 0.80 mmol), sodium acetate trihydrate (120 mg, 0.80 mmol), water (0.5 mL), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 25:1 dichloromethane/CH3OH to afford 232e as a yellow solid (180 mg, 55%). MS-ESI: [M+H]+ 636.3

Aufarbeitung

  1. customA round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated in vacuo
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 25:1 dichloromethane/CH3OH

Quellen und Nachweise

ORD-Eintrag
ord-6d2444c06b894ccbbd597346d737e692
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238655B2

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