Sodium Carbonate → N-tert-butyl-2-(isoquinolin-8-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246742Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246742
Br[C:2]1[N:7]=[C:6]2[C:8]([C:30]([NH:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:9][N:10](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:5]2=[N:4][CH:3]=1.N1[C:45]2[C:40](=[C:41](B(O)O)[CH:42]=[CH:43][CH:44]=2)[CH:39]=[N:38]1.[CH3:49][CH:50](C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:33]([NH:32][C:30]([C:8]1[C:6]2=[N:7][C:2]([C:41]3[CH:42]=[CH:43][CH:44]=[C:45]4[C:40]=3[CH:39]=[N:38][CH:50]=[CH:49]4)=[CH:3][N:4]=[C:5]2[NH:10][CH:9]=1)=[O:31])([CH3:35])([CH3:34])[CH3:36]

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 441183101H-Indazole-4-boronic acidHCID 866780082-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Produkt 1

HCID 71279452N-tert-butyl-2-(isoquinolin-8-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideAusbeute 292,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 2-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (0.5 g, 0.928 mmol), 1H-indazol-4-ylboronic acid (165 mg, 1.02 mmol), Pd(PPh3)4 (214 mg, 0.186 mmol), X-Phos (177 mg, 0.371 mmol) and Na2CO3 (295 mg, 2.78 mmol) in dioxane (20 mL) and water (5 mL) was heated to 100° C. for 16 hours under N2 atmosphere. Reaction mixture was concentrated and the residue was purified by preparative-TLC (eluting with methanol:dichloromethane=1:100) to afford N-tert-butyl-2-(isoquinolin-8-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (375 mg, 70%) as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 10.37 (s, 1H), 8.61 (s, 1H), 8.60 (s, 1H), 8.54 (s, 1H), 8.36 (s, 1H), 7.55-7.49 (m, 3H), 7.30-7.26 (m, 9H), 7.22-7.18 (m, 6H), 1.53 (s, 9H). LCMS: (M+H)+=577.

Aufarbeitung

  1. customReaction mixture
  2. concentrationwas concentrated
  3. customthe residue was purified by preparative-TLC (eluting with methanol:dichloromethane=1:100)

Quellen und Nachweise

ORD-Eintrag
ord-7fcb3b549f614543aad9c02e3b31a5a0
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

Notizen zur Reaktion

Wird geladen…