Triethylamine → 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 1890881ノート

反応式

HRID 1890881 の反応式
[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][N:9]2[C:14]3=[N:15][C:16]([Sn](C)(C)C)=[CH:17][N:18]=[C:13]3[NH:12][CH2:11][C:10]2=[O:23])[CH2:3][CH2:2]1.C(OC([N:31]1[C:35]2=[N:36][CH:37]=[CH:38][C:39](Br)=[C:34]2[CH:33]=[CH:32]1)=O)(C)(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>O1CCOCC1>[NH:31]1[C:35]2=[N:36][CH:37]=[CH:38][C:39]([C:16]3[N:15]=[C:14]4[N:9]([CH2:8][CH2:7][CH:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)[C:10](=[O:23])[CH2:11][NH:12][C:13]4=[N:18][CH:17]=3)=[C:34]2[CH:33]=[CH:32]1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 58298320tert-Butyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-1-carboxylateHCID 666067051-(2-(Tetrahydro-2H-pyran-4-yl)ethyl)-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

生成物 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-one収率 35%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
95 °C

実験手順

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]+.

後処理

  1. customwas purged
  2. customdegassed for 2 min
  3. customUpon completion of the reaction
  4. customthe volatiles were removed under reduced pressure
  5. customthe residue was purified by column chromatography

出典と根拠

ORDレコード
ord-8da5c5581fcc4452a70f4c69e83844eb
出典データセット
uspto-grants-2013_08
特許番号
US08507492B2

反応ノート

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