Methanol → HCID 22405715, Verbindung

HRID 441099

Reaktionsgleichung

Reaktionsgleichung von HRID 441099
[CH3:1][C:2]1[C:10]([NH:11][C:12]2[C:13](=[O:18])[C:14](=[O:17])[C:15]=2[CH3:16])=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:19][CH2:20][CH2:21]OS(C)(=O)=O)=[CH:5][NH:6]2.[CH3:27][O:28][C:29]1[C:30]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)=[N:31][CH:32]=[N:33][CH:34]=1.C(N(C(C)C)CC)(C)C.CO>C(#N)C.C(OCC)(=O)C>[NH4+:6].[OH-:17].[CH3:27][O:28][C:29]1[C:30]([N:35]2[CH2:40][CH2:39][N:38]([CH2:21][CH2:20][CH2:19][C:4]3[C:3]4[C:7](=[CH:8][CH:9]=[C:10]([NH:11][C:12]5[C:13](=[O:18])[C:14](=[O:17])[C:15]=5[CH3:16])[C:2]=4[CH3:1])[NH:6][CH:5]=3)[CH2:37][CH2:36]2)=[N:31][CH:32]=[N:33][CH:34]=1

Komponenten

8

Edukt 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 104201525-Methoxy-4-(piperazin-1-yl)pyrimidineHCID 22405702HCID 22405702, Verbindung

Produkt 2

HCID 14923Ammonium HydroxideHCID 22405715HCID 22405715, VerbindungAusbeute 155,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 4-methyl-5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)amino-3-(3-methanesulfonyloxypropyl)indole (0.154 g, 0.41 mmol), 1-(5-methoxy-4-pyrimidyl)piperazine (0.087 g, 0.45 mmol), finely pulverized KI (0.075 g, 0.45 mmol) and diisopropylethylamine (0.365 mL, 2.1 mmol) in 5 mL of acetonitrile was heated to reflux under Ar for 13 h. The resulting slurry was diluted with ethyl acetate, washed (H2O×2; brine), dried (Na2SO4) and evaporated to give a light brown gum. Flash chromatography of this gum (SiO2 /MeCN--MeOH--NH4OH, 90:9:1) afforded the title compound (0.151 g, 78%) as a pale yellow foam. A 142 mg sample of this material was taken up in methanol (ca. 3 mL) and 1N HCl (ca. 3 mL) was added. The resulting solution was concentrated and then stored at -20° C. to give a solid. This material was filtered, washed (1N HCl, acetone, ether) and then dried in vacuo to give the hydrochloride (0.140 g, 77%) as an off-white solid, mp >240° C. (dec): IR (KBr) 3400, 3200, 1784, 1722, 1595 cm-1 ; 1H NMR (DMSO-d6, 200 MHz) δ11.46 (br s, 1H), 11.09 (s, 0.7H), 11.01 (s, 0.3H), 10.62 (s, 0.7H), 10.46 (s, 0.3H), 8.62 (s, 1H), 8.21 (s, 1H), 7.24 (s, 1H), 7.22 (d, J=8.5 Hz, 0.7H), 7.16 (d, J=8.4 Hz, 0.3H), 6.95 (d, J=8.5 Hz, 0.7H), 6.88 (d, J=8.6 Hz, 0.3H), 4.88 (m, 2H), 3.91 (s, 3H), 3.66 (m, 4H), 3.17 (br s, 4H), 2.94 (m, 2H), 2.5-2.6 (m, 2H), 2.52 (s, 3H), 2.26 (s, 0.9H), 2.10 (m, 2H), 1.57 (s, 2.1H). Anal. Calcd for C26H30N6O3. 2 HCl. 1.7 H2O. 0.2 C2H3N. 0.25 C4H10O: C, 54.41; H, 6.42; N, 14.36. Found: C, 54.47; H, 6.80; N, 14.32.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux under Ar for 13 h
  3. washwashed (H2O×2; brine)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customto give a light brown gum

Quellen und Nachweise

ORD-Eintrag
ord-4da78be7218b4d86928ba472d2a298b3
Quelldatensatz
uspto-grants-1996_05
Patentnummer
US05521188

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