Phosphate → N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide

HRID 510212Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 510212
Cl[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]([NH:17][C@H:18]([C:22]([NH:24][CH2:25][C:26]([F:29])([F:28])[F:27])=[O:23])[CH:19]([CH3:21])[CH3:20])[CH:14]=[N:15][CH:16]=3)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]2=[N:6][CH:7]=1.[CH3:38][N:39]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[N:40]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:38][N:39]1[CH:43]=[C:42]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]4[CH:12]=[C:13]([NH:17][C@H:18]([C:22]([NH:24][CH2:25][C:26]([F:27])([F:28])[F:29])=[O:23])[CH:19]([CH3:21])[CH3:20])[CH:14]=[N:15][CH:16]=4)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]3=[N:6][CH:7]=2)[CH:41]=[N:40]1

Komponenten

8

Edukt 4

HCID 1061PhosphateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 131733258N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide

Produkt 1

HCID 131733262N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide 2-1a (200 mg, 0.360 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CA) (90 mg, 0.432 mmol), X-PHOS (30.9 mg, 0.065 mmol), palladium(II) acetate (9.69 mg, 0.043 mmol) in DMF (2 mL) was added phosphate tribasic (153 mg, 0.719 mmol) and water (0.4 mL). The mixture was evacuated then N2 purged 3 times and heated at 100° C. for overnight. After cooling the reaction was filtered and filtrate was loaded directly onto HPLC Reverse phase (C-18), eluting with acetonitrile/water (0.1% TFA), to give product 8-1a as a colorless foam. MS APCI: [M+H]+ m/z=602.1.

Aufarbeitung

  1. customThe mixture was evacuated
  2. customN2 purged 3 times
  3. temperatureAfter cooling the reaction
  4. filtrationwas filtered
  5. washeluting with acetonitrile/water (0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-6fecbb097ea84b67a7244eeb37fa0194
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096598B2

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