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 441087노트

반응식

HRID 441087 반응식
[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

참가 물질

7

반응물 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

생성물 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-indole수율 159.8%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a76292f572e44be3be89ae89da520c85
출처 데이터셋
uspto-grants-1996_05
특허 번호
US05521188

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