2-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide → N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246724

Reaktionsgleichung

Reaktionsgleichung von HRID 246724
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:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[F:37][CH:38]([F:62])[O:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][N:44]=[C:43]2[Sn](CCCC)(CCCC)CCCC>CN(C=O)C.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.[Cu]I>[C:33]([NH:32][C:30]([C:8]1[C:6]2=[N:7][C:2]([C:43]3[C:42]4[C:46](=[CH:47][CH:48]=[C:40]([O:39][CH:38]([F:37])[F:62])[CH:41]=4)[NH:45][N:44]=3)=[CH:3][N:4]=[C:5]2[N:10]([C:11]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:9]=1)=[O:31])([CH3:36])([CH3:34])[CH3:35]

Komponenten

6

Edukt 2

HCID 866780082-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideHCID 1784482315-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole

Produkt 1

HCID 71279313N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

In a round-bottomed flask, 2-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (530 mg, 1 mmol) and 5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole (470 mg, 1 mmol) were dissolved in DMF (10 mL) under nitrogen. Pd(PPh3)4 (58 mg, 0.05 mmol) and CuI (38 mg, 0.2 mmol) were added and mixture sonicated for 5 min while bubbling nitrogen. The reaction mixture was stirred at 80° C. for 4 hours. The concentrated mixture was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (3:1 to 1:1, v/v) to give N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (410 mg, 64%) as a solid. MS: (M+H)+=643.2; 1H NMR (300 MHz, CDCl3): δ 8.85 (d, 1H, J=2.4 Hz), 8.35 (s, 1H), 8.26 (s, 1H), 8.13 (s, 1H,), 7.52-7.48 (m, 1H), 6.51 (t, 1H, J=74.0 Hz), 1.60 (s, 9H).

Aufarbeitung

  1. custommixture sonicated for 5 min
  2. customwhile bubbling nitrogen
  3. customThe concentrated mixture was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (3:1 to 1:1

Quellen und Nachweise

ORD-Eintrag
ord-1c2e0ae735c5463091e1b7d166d3282b
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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