tert-Butyl 4-(7-oxo-8-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate → 7-(1H-Pyrrolo[2,3-b]pyridin-4-yl)-1-[2-(tetrahydro-pyran-4-yl)-ethyl]-3,4-dihydro-1H-pyrazino[2,3-b]pyrazin-2-one

HRID 1401227

Reaktionsgleichung

Reaktionsgleichung von HRID 1401227
[O:1]=[C:2]1[N:7]([CH2:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:6]2[N:16]=[C:17]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]4[N:26](C(OC(C)(C)C)=O)[CH:27]=[CH:28][C:21]=34)[CH:18]=[N:19][C:5]=2[NH:4][CH2:3]1>Cl>[NH:26]1[C:22]2=[N:23][CH:24]=[CH:25][C:20]([C:17]3[N:16]=[C:6]4[N:7]([CH2:8][CH2:9][CH:10]5[CH2:15][CH2:14][O:13][CH2:12][CH2:11]5)[C:2](=[O:1])[CH2:3][NH:4][C:5]4=[N:19][CH:18]=3)=[C:21]2[CH:28]=[CH:27]1

Komponenten

3

Edukt 1

HCID 86644653tert-Butyl 4-(7-oxo-8-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Produkt 1

HCID 462158977-(1H-Pyrrolo[2,3-b]pyridin-4-yl)-1-[2-(tetrahydro-pyran-4-yl)-ethyl]-3,4-dihydro-1H-pyrazino[2,3-b]pyrazin-2-oneAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 313Hydrochloric AcidLösungsmittel

Versuchsvorschrift

A mixture of 1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (See Example 15.C) (1 equiv), 4-bromo-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (1 equiv), tris(dibezylideneacetone) palladium (0.13 equiv), tri-o-tolylphosphine (0.25 equiv) and triethylamine (2.8 equiv) in anhydrous dioxane was purged, degassed for 2 min and stirred at 95° C. under nitrogen for 3-4 h. Upon completion of the reaction as indicated by TLC, the volatiles were removed under reduced pressure and the residue was purified by column chromatography to give the desired product in 35% yield. MS (ESI) m/z 479.7 [M+1]+. tert-Butyl 4-(7-oxo-8-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate was stirred in methanolic hydrochloride solution at room temperature. Upon completion of the reaction as indicated by TLC, the solvent was removed under reduced pressure and the residue was purified on silica gel to give the title compound in 63% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 11.72 (s, 1H), 8.38 (s, 1H), 8.25 (d, J=4.8 Hz, 1H), 7.79 (s, 1H), 7.53-7.51 (m, 2H), 6.97 (q, J=1.6 Hz, 1H), 4.23 (s, 2H), 4.14 (t, J=7.6 Hz, 2H), 3.81 (dd, J1=2.4 Hz, J2=11.2 Hz, 2H), 3.25 (d, J=10.8 Hz, 2H), 1.67 (d, J=13.2 Hz, 2H), 1.61 (m, 3H), 1.22 (m, 2H); MS (ESI): m/z 379.2 [M+1]+.

Aufarbeitung

  1. customUpon completion of the reaction
  2. customthe solvent was removed under reduced pressure
  3. customthe residue was purified on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-05d6da69ebae42b9ae67363d9bc411e0
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08907087B2

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