Potassium Phosphate, Tribasic → 2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

HRID 1411590Notizen

Reaktionsgleichung

[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:27]=[C:21]3[CH2:22][N:23]([CH3:26])[CH2:24][CH2:25][N:20]3[N:19]=2)[C:3]1=[O:28].Cl[C:30]1[C:35]([CH:36]=[O:37])=[C:34]([N:38]2[CH2:51][CH2:50][N:41]3[C:42]4[CH2:43][CH2:44][CH2:45][CH2:46][C:47]=4[C:48]([F:49])=[C:40]3[C:39]2=[O:52])[N:33]=[CH:32][CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>CC#N.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]>[F:49][C:48]1[C:47]2[CH2:46][CH2:45][CH2:44][CH2:43][C:42]=2[N:41]2[CH2:50][CH2:51][N:38]([C:34]3[N:33]=[CH:32][CH:31]=[C:30]([C:6]4[CH:5]=[C:4]([NH:17][C:18]5[CH:27]=[C:21]6[CH2:22][N:23]([CH3:26])[CH2:24][CH2:25][N:20]6[N:19]=5)[C:3](=[O:28])[N:2]([CH3:1])[CH:7]=4)[C:35]=3[CH:36]=[O:37])[C:39](=[O:52])[C:40]=12

Komponenten

Reaktionsbedingungen

Temperatur: 100 °C

Versuchsvorschrift

A suspension of 135a (385 mg, 1 mmol), 4-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde 134c (347 mg, 1 mmol), K3PO4 (424 mg, 2 mmol), NaOAc (164 g, 2 mmol) and 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (41 mg, 0.05 mmol) in CH3CN (50 ml) was heated at 100° C. under an N2 balloon for 4 h. Analysis of reaction mixture by LCMS showed completed conversion to the desired product. The reaction mixture was cooled to room temperature and diluted with DCM (50 ml) and water (80 mL). The aqueous layer was separated and extracted with DCM (3×50 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated. The dark residue was purified by silica gel column chromatography eluting with DCM/MeOH (from 80/1 to 30/1) to afford 135b (285 g, 50%) as yellow solid. MS: [M+H]+ 571

Aufarbeitung

customAnalysis of reaction mixture by LCMS

Quellen und Nachweise

ORD-Eintrag: ord-eede6875278d494b94036657d5d3d066
Quelldatensatz: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08921353B2

Notizen zur Reaktion

Wird geladen…