Methanol → 4-Chloro-6-methyl-10,10-dioxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1172515Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1172515
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1.Cl[CH2:10][CH2:11][N:12]([CH2:35][CH2:36]Cl)[C:13]1[CH:33]=[C:32]([Cl:34])[C:16]2[O:17][C:18]3[C:27]([CH3:28])=[CH:26][C:25]([C:29]([OH:31])=[O:30])=[CH:24][C:19]=3[S:20](=[O:23])(=[O:22])[CH2:21][C:15]=2[CH:14]=1.[CH3:38]O>>[CH3:38][O:31][C:29]([C:25]1[CH:26]=[C:27]([CH3:28])[C:18]2[O:17][C:16]3[C:32]([Cl:34])=[CH:33][C:13]([N:12]4[CH2:11][CH2:10][N:1]([CH2:2][CH2:3][N:4]5[CH2:8][CH2:7][CH2:6][CH2:5]5)[CH2:36][CH2:35]4)=[CH:14][C:15]=3[CH2:21][S:20](=[O:23])(=[O:22])[C:19]=2[CH:24]=1)=[O:30]

Komponenten

4

Edukt 3

HCID 887MethanolHCID 13441-PyrrolidineethanamineHCID 1317284742-[Bis-(2-chloroethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid

Produkt 1

HCID 1317284854-Chloro-6-methyl-10,10-dioxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

1-(2-Aminoethyl)pyrrolidine (1.60 mL, 12.6 mmol) was added to a solution of Example 102j (0.75 g, 1.50 mmol) in methanol (5 mL), in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 110° C. for 5 h. The reaction mixture was brought to room temperature, concentrated, treated with methanolic HCl solution, and refluxed at 70° C. for 2 h. The reaction mixture was concentrated, treated with aqueous sodium bicarbonate solution to neutral pH and extracted with n-butanol. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, 5% methanol/chloroform) to obtain the title compound. Yield: 0.320 g, (30.5%); 1H NMR (DMSO-d6): δ 1.90-1.95 (m, 4H, 2CH2), 2.62 (s, 6H, 2CH3), 2.70 (s, 3H, CH3), 3.10-3.15 (m, 8H, 4CH2), 3.20-3.25 (m, 4H, 2CH2), 3.90 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.20 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.15 (s, 1H, Ar); MS : m/e (CI+) 534 (M+).

Aufarbeitung

  1. customsealed in a pressure reactor vessel at 110° C. for 5 h
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with methanolic HCl solution
  5. concentrationThe reaction mixture was concentrated
  6. additiontreated with aqueous sodium bicarbonate solution to neutral pH
  7. extractionextracted with n-butanol
  8. washThe organic layer was washed with water, brine
  9. customdried
  10. concentrationconcentrated
  11. custompurified

Quellen und Nachweise

ORD-Eintrag
ord-31a38847016a477ab2d06644d27fdcf6
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07834001B2

Notizen zur Reaktion

Wird geladen…