Diisopropylethylamine → 3-[3-[4-(5-Methoxy-4-pyrimidyl)-1-piperazinyl]propyl]-5-(1,2-dioxo-4-methylamino-3-cyclobuten-3-yl)-1-triisopropylsilyl-1H-indole

HRID 441087ノート

反応式

HRID 441087 の反応式
[O:1]=[C:2]1[C:5]([NH:6][C:7](C)(C)C)=[C:4]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([Si:20]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH:15]=[C:14]3[CH2:30][CH2:31][CH2:32]OS(C2C=CC(C)=CC=2)(=O)=O)[C:3]1=[O:44].C[CH:46]1[NH:51][CH2:50][CH2:49][N:48]([C:52]2[C:57]([O:58][CH3:59])=[CH:56][N:55]=[CH:54][N:53]=2)[CH2:47]1.C(N(C(C)C)CC)(C)C>C(#N)C.C(OCC)(=O)C>[NH4+:6].[OH-:1].[CH3:59][O:58][C:57]1[C:52]([N:48]2[CH2:49][CH2:50][N:51]([CH2:32][CH2:31][CH2:30][C:14]3[C:13]4[C:17](=[CH:18][CH:19]=[C:11]([C:4]5[C:3](=[O:44])[C:2](=[O:1])[C:5]=5[NH:6][CH3:7])[CH:12]=4)[N:16]([Si:20]([CH:27]([CH3:28])[CH3:29])([CH:21]([CH3:23])[CH3:22])[CH:24]([CH3:25])[CH3:26])[CH:15]=3)[CH2:46][CH2:47]2)=[N:53][CH:54]=[N:55][CH:56]=1

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 150205455-Methoxy-4-(3-methylpiperazin-1-yl)pyrimidineHCID 224057045-[1,2-Dioxo-4-t-butylamino-3-cyclobuten-3-yl]-3-[3-(p-toluenesulfonyl)oxypropyl]-1-triisopropylsilyl-1H-indole

生成物 2

HCID 14923Ammonium HydroxideHCID 224056983-[3-[4-(5-Methoxy-4-pyrimidyl)-1-piperazinyl]propyl]-5-(1,2-dioxo-4-methylamino-3-cyclobuten-3-yl)-1-triisopropylsilyl-1H-indole収率 159.8%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 5-(1,2-dioxo-4-methylamino-3-cyclobuten-3-yl)-3-[3-(p-toluenesulfonyl)oxypropyl]-1-triisopropylsilylindole (14) 0.247 g, 0.42 mmol), 1-(5-methoxy-4-pyrimidyl)piperazine (1) (0.081 g, 0.42 mmol), finely pulverized KI (0.070 g, 0.42 mmol) and diisopropylethylamine (0.37 mL, 2.1 mmol) in 10 mL of acetonitrile was heated to reflux under Ar for 18 h. The cooled reaction mixture was diluted with ethyl acetate and washed with water. The aqueous phase was back-extracted with dichloromethane (2×) and the combined organic phase was dried (Na2SO4) and evaporated to give a yellow foam. The foam was chromatographed (SiO2 /ethyl acetate--MeOH--NH4OH, 90:9:1 then MeCN--MeOH--NH4OH, 90:9:1) to give the title compound (0.207 g, 80%) as a yellow foam: IR (neat) 3280 (br), 1770, 1720, 1595 (br), 1140 cm-1 ; 1H NMR (CDCl3, 200 MHz) δ 8.34 (s, 1H), 8.08 (d, J=1.5 Hz, 1H), 7.92 (s, 1H), 7.75 (m, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.06 (s, 1H), 6.8 (br s, 1H), 3.90 (br s, 2H), 3.86 (s, 3H), 3.51 (d, J=4.9 Hz, 2H), 3.41 (d, J=4.9 Hz, 1H), 3.2-2.8 (m, 4H), 2.8-2.6 (m, 4H), 2.4-2.0 (m, 4H), 1.67 (hept, J=7.5 Hz, 3H), 1.13 (d, J=7.5 Hz, 18H).

後処理

  1. temperaturewas heated
  2. temperatureto reflux under Ar for 18 h
  3. customThe cooled reaction mixture
  4. washwashed with water
  5. extractionThe aqueous phase was back-extracted with dichloromethane (2×)
  6. dry with materialthe combined organic phase was dried (Na2SO4)
  7. customevaporated
  8. customto give a yellow foam
  9. customThe foam was chromatographed (SiO2 /ethyl acetate

出典と根拠

ORDレコード
ord-a76292f572e44be3be89ae89da520c85
出典データセット
uspto-grants-1996_05
特許番号
US05521188

反応ノート

読み込み中…