Potassium Phosphate, Tribasic → (S)-(2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1022009Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1022009
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:15]2[CH2:28][CH2:27][N:18]3[C:19]4[CH2:20][CH2:21][CH2:22][CH2:23][C:24]=4[C:25]([F:26])=[C:17]3[C:16]2=[O:29])=[N:8][CH:9]=[CH:10][C:11]=1B(O)O)(=[O:3])[CH3:2].Cl[C:31]1[CH:32]=[C:33]([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:34](=[O:38])[N:35]([CH3:37])[N:36]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([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].O.C(#N)C>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:15]2[CH2:28][CH2:27][N:18]3[C:19]4[CH2:20][CH2:21][CH2:22][CH2:23][C:24]=4[C:25]([F:26])=[C:17]3[C:16]2=[O:29])=[N:8][CH:9]=[CH:10][C:11]=1[C:31]1[CH:32]=[C:33]([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][C@@H:47]3[CH3:56])=[CH:42][N:41]=2)[C:34](=[O:38])[N:35]([CH3:37])[N:36]=1)(=[O:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 86683946(S)-6-Chloro-2-methyl-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-oneHCID 866844343-(Acetoxymethyl)-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic Acid

Produkt 1

HCID 86684435(S)-(2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl AcetateAusbeute 60 %

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 231c (200 mg, 0.50 mmol), (S)-6-chloro-2-methyl-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one 224c (195 mg, 0.50 mmol), PdCl2(dppf) (24 mg, 0.030 mmol), K3PO4 (212 mg, 1.0 mmol), sodium acetate (98 mg, 1.0 mmol), acetonitrile (30 mL), and water (3 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 1:3 petroleum/ethyl acetate to afford 231d as a yellow solid (213 mg, 60%). MS-ESI: [M+H]+ 712.3

Aufarbeitung

  1. customA round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was evaporated under reduced pressure
  6. customThe residue was purified with silica-gel column chromatography
  7. washeluting with 1:3 petroleum/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-1f3a0594607c4ebbb3b209cfaefa6cb3
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716274B2

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