Sodium Thiosulfate → 1-(3-Benzoyl-thioureido)-4-bromo-1H-pyrrole-2-carboxylic acid methyl ester

HRID 1262276Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1262276
NCl.CC1C=CC(S([N:13](C)C)(=O)=O)=CC=1C1N2C(C=NC(NC3C=CC(N4CCN(C)CC4)=CC=3)=N2)=CC=1.[CH3:39][O:40][C:41]([C:43]1[NH:44][CH:45]=[C:46]([Br:48])[CH:47]=1)=[O:42].CC(C)([O-])C.[K+].[O-]S([O-])(=S)=O.[Na+].[Na+].[C:62]([N:70]=[C:71]=[S:72])(=[O:69])[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1>CCOCC.O1CCCC1>[CH3:39][O:40][C:41]([C:43]1[N:44]([NH:13][C:71]([NH:70][C:62](=[O:69])[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)=[S:72])[CH:45]=[C:46]([Br:48])[CH:47]=1)=[O:42]

Komponenten

9

Edukt 6

HCID 24477Sodium ThiosulfateHCID 25423Monochloramine2×HCID 68284Benzoyl isothiocyanateHCID 2763594Methyl 4-bromo-1H-pyrrole-2-carboxylateHCID 23665647Potassium tert-butoxideHCID 667110074,N,N-Trimethyl-3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzenesulfonamide

Produkt 1

HCID 866616921-(3-Benzoyl-thioureido)-4-bromo-1H-pyrrole-2-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

Chloramine was made according to J. Org. Chem., Vol 69 (4), 1368-1371. Into 4 L Erlenmyer flask, 4-Bromo-1H-pyrrole-2-carboxylic acid methyl ester (30.0 g, 0.147 mol) and Tetrahydrofuran (800 mL, 9 mol) were added and stirred at RT for 20 minutes under an atmosphere of Nitrogen. 1.00 M of Potassium tert-Butoxide in Tetrahydrofuran (379 mL, 0.379 mol) was added and stirred for 30 minutes at room temperature. 0.15 M of Chloramine in Ether (1570 mL) was added to the reaction mixture at 10° C. over 20 minutes with nitrogen bubbling into the reaction mixture. The reaction was stirred at room temperature for 2 hours. HPLC suggested 72% conversion (18% SM remained). Saturated Na2S2O3 (500 mL) was added at 10° C. over 30 minutes. The mixture was stirred for one hour. The organic was separated, washed with water, then subsequently with Brine, and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was concentrated to approximately 500 mL. Benzoyl isothiocyanate (17.26 g, 0.1058 mol) in Tetrahydrofuran (80 mL) was added dropwise to the residual organic. The reaction mixture was stirred at room temperature overnight. The solvent was removed under vacuum. The solid was partitioned with Et2O (200 mL) and stirred for 30 minutes. The solid was filtered and washed with hexane/Et2O (9 to 1) to give 1-(3-Benzoyl-thioureido)-4-bromo-1H-pyrrole-2-carboxylic acid methyl ester an off white solid (31.20, 55%).

Aufarbeitung

  1. stirringstirred for 30 minutes at room temperature
  2. stirringThe reaction was stirred at room temperature for 2 hours
  3. stirringThe mixture was stirred for one hour
  4. customThe organic was separated
  5. washwashed with water
  6. dry with materialsubsequently with Brine, and dried over Na2SO4
  7. filtrationThe solid was filtered
  8. washwashed with DCM
  9. concentrationThe solvent was concentrated to approximately 500 mL
  10. stirringThe reaction mixture was stirred at room temperature overnight
  11. customThe solvent was removed under vacuum
  12. customThe solid was partitioned with Et2O (200 mL)
  13. stirringstirred for 30 minutes
  14. filtrationThe solid was filtered
  15. washwashed with hexane/Et2O (9 to 1)

Quellen und Nachweise

ORD-Eintrag
ord-fd35e7c9f11742e2afab0328a97a1119
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08471005B2

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