Chlorosulfonyl isocyanate → Methyl 3-[[(4-methoxy-6-methyl-pyrimidine-2-yl)aminocarbonyl]aminosulfonyl]-1-methyl-1H-indole-2-carboxylate

HRID 1904170

Reaktionsgleichung

Reaktionsgleichung von HRID 1904170
[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([CH3:10])[N:3]=1.Cl[S:12]([N:15]=[C:16]=[O:17])(=[O:14])=[O:13].[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20]1[C:28]([O:30][CH3:31])=[O:29].[Cl-].[Al+3].[Cl-].[Cl-]>C[N+]([O-])=O.ClCCl.O>[CH3:9][O:8][C:6]1[CH:5]=[C:4]([CH3:10])[N:3]=[C:2]([NH:1][C:16]([NH:15][S:12]([C:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:19]([CH3:18])[C:20]=2[C:28]([O:30][CH3:31])=[O:29])(=[O:14])=[O:13])=[O:17])[N:7]=1

Komponenten

8

Edukt 4

HCID 70918Chlorosulfonyl isocyanateHCID 258548methyl 1-methyl-1H-indole-2-carboxylateHCID 5872364-Methoxy-6-methylpyrimidin-2-amineHCID 6451240Aluminum(III) Chloride

Produkt 1

HCID 14256296Methyl 3-[[(4-methoxy-6-methyl-pyrimidine-2-yl)aminocarbonyl]aminosulfonyl]-1-methyl-1H-indole-2-carboxylateAusbeute 17,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 6375NitromethaneLösungsmittel2×

Versuchsvorschrift

To a stirred suspension of 2.92 g (0.021 mole) of 2-amino-4-methoxy-6-methylpyrimidine in 75 ml dry CH3NO2 at -10° was added dropwise under nitrogen via syringe 2.0 ml (0.023 mole) of chlorosulfonyl isocyanate at such a rate as to maintain the temperature below 0°. The resulting clear solution was stirred 0.5 hour at -5° to -10° and then contacted dropwise with a solution of 3.97 g (0.021 mole) of methyl 1-methyl-1H-indole-2-carboxylate dissolved in 25 ml of dry nitromethane. Upon completion of the addition, 2.95 g (0.022 mole) of aluminum (III) chloride was added in one portion. The reaction mixture was stirred at reflux for 3 hours, then cooled to room temperature and poured into 300 ml H2O. Dichloromethane was added and the layers were separated. The aqueous solution was extracted with two additional portions of CH4Cl2 and the combined organic solutions washed with H2O, dried over MgSO4 and evaporated in vacuo. Chromatography on silica gel with 5% acetone in CH2Cl2 afforded 1.63 g of the desired product as a white solid, m.p. 200°-203° (d). The infrared spectrum of the product included absorptions at 3190 (NH), 1715 (C=O), 1703 (C=O), 1340 and 1150 (SO2) cm-1, 'H NMR (CDCl3 /DMSO-d6) δ2.45 (s, 3H, pyrimidine CH3), 3.95 (s, 3H, OCH3), 4.0 (s, 6H, OCH3N--CH3), 6.37 (s, 1H, pyrimidine CH), 7.23-7.56 (m, 3H, indole CH), 8.18-8.47 (m, 1H, indole CH), 9.50 (s, 1H, NH), 13.08 (br s, 1H, NH). Mass spectral analysis showed m/e 139, ##STR31##

Aufarbeitung

  1. temperatureto maintain the temperature below 0°
  2. additionwas added in one portion
  3. stirringThe reaction mixture was stirred
  4. temperatureat reflux for 3 hours
  5. customthe layers were separated
  6. extractionThe aqueous solution was extracted with two additional portions of CH4Cl2
  7. washthe combined organic solutions washed with H2O
  8. dry with materialdried over MgSO4
  9. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-701c4f01bc734904a1509a6176ab92cf
Quelldatensatz
uspto-grants-1989_06
Patentnummer
US04836846

Verknüpfte Notizen

Wird geladen…