Ethyl Acetate → Tert-butyl 3-{5-[5-chloro-2-(4-{[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)amino]sulfonyl}-2,5-difluorophenoxy)phenyl]-1H-pyrazol-1-yl}azetidine-1-carboxylate

HRID 46371

Reaktionsgleichung

Reaktionsgleichung von HRID 46371
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:24])=[C:6]([C:8]2[N:12]([CH:13]3[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]3)[N:11]=[CH:10][CH:9]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:31][O:32][C:33]1[CH:57]=[C:56]([O:58][CH3:59])[CH:55]=[CH:54][C:34]=1[CH2:35][N:36]([C:49]1[S:53][N:52]=[CH:51][N:50]=1)[S:37]([C:40]1[CH:45]=[C:44]([F:46])[C:43](F)=[CH:42][C:41]=1[F:48])(=[O:39])=[O:38].C(OCC)(=O)C>CS(C)=O.ClCCl.C(OC)(C)(C)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][C:43]2[CH:42]=[C:41]([F:48])[C:40]([S:37]([N:36]([CH2:35][C:34]3[CH:54]=[CH:55][C:56]([O:58][CH3:59])=[CH:57][C:33]=3[O:32][CH3:31])[C:49]3[S:53][N:52]=[CH:51][N:50]=3)(=[O:38])=[O:39])=[CH:45][C:44]=2[F:46])=[C:6]([C:8]2[N:12]([CH:13]3[CH2:14][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:16]3)[N:11]=[CH:10][CH:9]=2)[CH:7]=1

Komponenten

9

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 59436583N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 136063615tert-butyl 3-(5-(5-chloro-2-hydroxyphenyl)-1H-pyrazol-1-yl)azetidine-1-carboxylate

Produkt 1

HCID 59436544Tert-butyl 3-{5-[5-chloro-2-(4-{[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)amino]sulfonyl}-2,5-difluorophenoxy)phenyl]-1H-pyrazol-1-yl}azetidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Versuchsvorschrift

Tert-butyl 3-[5-(5-chloro-2-hydroxyphenyl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (Preparation 851, 80.0 g, 0.2287 mol) and potassium carbonate (94.82 g, 0.686 mol) were combined in dimethylsulphoxide (600 mL). To this slurry was added N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide, (Preparation 647, 101.87 g, 0.2287 mol) and stirred at room temperature for 4.5 hours. Ethyl acetate (1600 mL) and water (1000 mL) were added and the layers separated. The ethyl acetate was washed with water (2×800 mL), then saturated aqueous sodium chloride solution (200 mL) and then dried over anhydrous magnesium sulphate. To this suspension, tert-butylmethyl ether (250 mL) was added and the mixture was washed with dilute aqueous sodium chloride solution (1000 mL), the organics were dried over magnesium sulphate, filtered and the solvents removed in-vacuo to give a pale yellow solid. This solid was dissolved in dichloromethane (500 mL) and tert-butylmethyl ether was added gradually whilst evaporating the dichloromethane in vacuo to give a white precipitate which was filtered off and washed with a little tert-butylmethyl ether to give the title compound as a white solid, (145.47 g).

Aufarbeitung

  1. additionTo this slurry was added
  2. customthe layers separated
  3. washThe ethyl acetate was washed with water (2×800 mL)
  4. dry with materialsaturated aqueous sodium chloride solution (200 mL) and then dried over anhydrous magnesium sulphate
  5. additionTo this suspension, tert-butylmethyl ether (250 mL) was added
  6. washthe mixture was washed with dilute aqueous sodium chloride solution (1000 mL)
  7. dry with materialthe organics were dried over magnesium sulphate
  8. filtrationfiltered
  9. customthe solvents removed in-vacuo
  10. customto give a pale yellow solid
  11. customwhilst evaporating the dichloromethane in vacuo
  12. customto give a white precipitate which
  13. filtrationwas filtered off
  14. washwashed with a little tert-butylmethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-93f39d2b7a0f41a58eed4ea333113efc
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541588B2

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