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

HRID 907762Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 907762
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. additionwere added to the reaction mixture
  5. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-d350306092df444eb1083c9609cc8d6e
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08013166B2

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