Hydrochloric Acid → cis-3-[4'-(6-Chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid

HRID 30939Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 30939
C[O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)=[O:12])[CH2:6]1)=[O:4].Cl[C:27]1[S:28][C:29]2[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:30]=2[N:31]=1.[OH-].[Na+].Cl>C(O)CCC.Cl.O1CCOCC1.CO>[Cl:36][C:34]1[CH:33]=[CH:32][C:30]2[N:31]=[C:27]([NH:25][C:22]3[CH:21]=[CH:20][C:19]([C:16]4[CH:17]=[CH:18][C:13]([C:11]([C@@H:7]5[CH2:8][CH2:9][CH2:10][C@H:5]([C:3]([OH:4])=[O:2])[CH2:6]5)=[O:12])=[CH:14][CH:15]=4)=[CH:24][CH:23]=3)[S:28][C:29]=2[CH:35]=1

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 771762,6-Dichlorobenzothiazole2×HCID 235493393-(4'-Amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester

Produkt 1

HCID 11698838cis-3-[4'-(6-Chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acidAusbeute 23,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 313Hydrochloric AcidKatalysator2×HCID 2631-ButanolLösungsmittelHCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of 3-(4′-amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester (100 mg, 0.3 mmol) in butanol (5 mL), 2,6-dichloro-benzothiazole (60 mg, 0.3 mmol) and 5 drops of 4 M HCl in dioxane were added, and the reaction mixture was heated at 90° C. for 5 h. An additional sample of 2,6-dichlorobenzothiazole (60 mg, 0.3 mmol) and 5 drops of 4 M HCl in dioxane were then added, and the reaction mixture was heated overnight at 90° C. The solvent was removed by rotary evaporation, the residue was dissolved in DMF (2 mL), 1 N aqueous NaOH (0.3 mL, 0.3 mmol) was added, and the mixture was heated at 75° C. overnight. A solution of 1 N aqueous HCl (0.3 mL, 0.3 mmol) and methanol (5 mL) were added to the reaction mixture, and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford cis-3-[4′-(6-chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid as a white solid (12.6 mg, yield 23.4%). 1H NMR (300 MHz, DMSO) δ 8.05 (d, 2H), 7.75-8.00 (m, 7H), 7.50 (d, 1H), 7.35 (d, 1H), 3.25 (m, 1H), 2.50 (m, 1H), 2.20-1.90 (m, 4H), 1.70-1.50 (m, 4H); LC-MS ret. time 3.99 min (method 2), m/z 491.11 (MH+).

Aufarbeitung

  1. temperaturethe reaction mixture was heated overnight at 90° C
  2. customThe solvent was removed by rotary evaporation
  3. dissolutionthe residue was dissolved in DMF (2 mL)
  4. temperaturethe mixture was heated at 75° C. overnight
  5. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-deb39dc57d4944fcb43f68c76556a939
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423156B2

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