Hexamethylditin → N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246482Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246482
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.C[Sn](C)C.C[Sn](C)C.Br[C:35]1[N:36]=[CH:37][CH:38]=[C:39]2[CH:43]=[CH:42][N:41]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:40]=12>C1(C)C=CC=CC=1.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:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:35]3[N:36]=[CH:37][CH:38]=[C:39]4[CH:43]=[CH:42][N:41]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:40]=34)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Komponenten

6

Edukt 3

HCID 6327618HexamethylditinHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 866779827-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine

Produkt 1

HCID 71279899N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.2 g, 468 μmol) and hexamethylditin (215 mg, 655 mmol) in toluene (2.5 mL) was added Pd(Ph3P)4 (54 mg). After bubbling nitrogen through the reaction mixture for 15 min, it was heated to 95° C. After 1.5 h, 7-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine and Pd(Ph3P)4 (108 mg, 93.6 μmol) were added. After 72 h the reaction mixture was cooled, filtered through celite, and concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.13 g, 47%). 1H NMR (CDCl3) δ: 9.01 (s, 1H), 8.46 (d, J=5.3 Hz, 1H), 8.34 (s, 1H), 8.13 (s, 1H), 7.68 (d, J=5.3 Hz, 1H), 7.41 (d, J=3.0 Hz, 1H), 6.69 (d, J=3.3 Hz, 1H), 5.74 (s, 2H), 5.51 (s, 2H), 3.59 (dd, J=8.9, 7.7 Hz, 2H), 2.82-2.89 (m, 2H), 1.42 (s, 9H), 0.92-0.99 (m, 2H), 0.41-0.47 (m, 2H), −0.02 (s, 9H), −0.27 (s, 9H).

Aufarbeitung

  1. customAfter bubbling nitrogen through the reaction mixture for 15 min
  2. temperatureAfter 72 h the reaction mixture was cooled
  3. filtrationfiltered through celite
  4. concentrationconcentrated in vacuo
  5. customPurification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-b214346bec9e44ee957d02ee3b740ef0
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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