Nitrogen → HCID 53629073、化合物

HRID 422708ノート

反応式

HRID 422708 の反応式
I[C:2]1[N:3]=[C:4]([CH:12]2[CH2:15][CH:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.[F:23][C:24]1[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:27]=[C:28]2[C:33]=1[N:32]=[C:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH:30]=[CH:29]2.C(=O)([O-])[O-].[Cs+].[Cs+].N#N.C([O-])(O)=O.[Na+]>COCCOC.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>[F:23][C:24]1[C:25]([C:2]2[N:3]=[C:4]([CH:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)[CH2:13]3)[N:5]3[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=23)=[CH:26][CH:27]=[C:28]2[C:33]=1[N:32]=[C:31]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH:30]=[CH:29]2

参加物

9

反応物 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 536290468-Fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinolineHCID 576810251-Iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine

生成物 1

HCID 53629073HCID 53629073、化合物

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
75 °C

実験手順

A solution of 1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine (93 mg, 0.22 mmol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline (87 mg, 0.25 mmol) and cesium carbonate (88 mg, 0.27 mmol) in DME (3.33 mL) and H2O (0.67 mL) was degassed with N2 for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.011 mmol) was added, and the reaction heated at 75° C. overnight. The reaction was allowed to cool to rt, poured into saturated NaHCO3 solution (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organics were washed with brine (3×50 ml), dried (MgSO4), filtered and concentrated in vacuo. Flash chromatography (DCM stepping up to 5% MeOH in DCM) gave the title compound as an off-white solid; 1H NMR (CDCl3, 400 MHz) δ 8.27 (1H, d, J=8.6 Hz), 8.23 (2H, d, J=7.1 Hz), 7.99 (1H, d, J=8.8 Hz), 7.73-7.67 (2H, m), 7.55-7.48 (3H, m), 7.16 (1H, d, 5.1 Hz), 7.06 (1H, d, J=5.1 Hz), 3.46 (1H, m), 2.94 (1H, m), 2.71-2.32 (15H, m); MS (ES+): m/z 508.03 [MH+]; HPLC: tR=1.71 min (MicromassZQ, polar—5 min).

後処理

  1. temperatureto cool to rt
  2. extractionextracted with ethyl acetate (3×50 ml)
  3. washThe combined organics were washed with brine (3×50 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-cf28da9cabf247ab978a4723c4ca379e
出典データセット
uspto-grants-2012_01
特許番号
US08101613B2

反応ノート

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