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 441087Notes

Reaction equation

HRID 441087 reaction equation
[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

Participants

7

Reactant 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

Product 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-indoleYield 159.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a76292f572e44be3be89ae89da520c85
Source dataset
uspto-grants-1996_05
Patent number
US05521188

Reaction notes

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