Hydrochloric Acid → 2-Carboxy-7-chloro-4-methylthioquinoline

HRID 890415Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 890415
C[O:2][C:3]([C:5]1[CH:14]=[C:13]([S:15][CH3:16])[C:12]2[C:7](=[CH:8][C:9]([Cl:17])=[CH:10][CH:11]=2)[N:6]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1.O>[C:3]([C:5]1[CH:14]=[C:13]([S:15][CH3:16])[C:12]2[C:7](=[CH:8][C:9]([Cl:17])=[CH:10][CH:11]=2)[N:6]=1)([OH:4])=[O:2]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 221848242-(Methoxycarbonyl)-7-chloro-4-methylthioquinoline

Produkt 1

HCID 221847702-Carboxy-7-chloro-4-methylthioquinolineAusbeute 76,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21881883Oxolane--water (1/1)Lösungsmittel

Versuchsvorschrift

To a solution of 2-carboxy-7-chloro-4-mercaptoquinoline HCl salt (75 mg, 0.31 mmol) in DMF (3 mL) was added MeI (0.0425 mL, 2.5 eq.) and cesium carbonate (340 mg, 3.5 eq.). The resulting reaction mixture was stirred at 70° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with water, brine, and dried over sodium sulfate. The solvent was evaporated. Flash column chromatograpgy with 1%–2% MeOH in methylene chloride afforded 2-(methoxycarbonyl)-7-chloro-4-methylthioquinoline (40 mg). To 2-(methoxycarbonyl)-7-chloro-4-methylthioquinoline (40 mg) was added THF:H2O (2:1, 2 mL) and LiOH (10 mg, 1.5 eq.). The reaction mixture was stirred for 2 hours. The pH was adjusted to pH 4.5 with 1N HCl. Extraction with ethyl acetate, washing with brine, drying over sodium sulfate and evaporation gave 2-carboxy-7-chloro-4-methylthioquinoline (29 mg). To a solution of 2-carboxy-7-chloro-4-methylthioquinoline (29 mg) in THF (6 mL) and DMF (1 mL) was added 4-ethoxycarbonyl-1-(1-amino-3-(1,1-dimethylethoxycarbonyl)propyl)carbonylpiperazine (46 mg, 1.1 eq.), EDCl (28 mg, 1.2 eq.), and HOBt (18 mg, 1.1 eq.). The resulting reaction mixture was stirred at ambient temperature overnight. The reaction mixture was evaporated in vacuo to afford a crude product, which was dissolved in ethyl acetate, washed with saturated NaHCO3, 1M NaHSO4 and brine. The organic layer was evaporated. Flash column chromatography with 1%–3% MeOH in CH2Cl2 afforded the product, 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(1,1-dimethylethoxycarbonyl)propyl]aminocarbonyl-7-chloro-4-(methylthio)quinoline (36 mg). The product (32 mg) was treated with TFA:CH2Cl2 (1:1, 1 mL) at ambient temperature for 2 hours. The solvents were then evaporated to afford the desired product, 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-carboxypropyl]aminocarbonyl-7-chloro-4-(methylthio)quinoline; NMR (CDCl3) 1.35 (t, 3), 2.10 (m, 1), 2.25 (m, 1), 2.55 (m, 2), 2.7 (s, 3), 3.4–3.9 (m, 8), 4.2 (q, 2), 5.3 (m, 1), 7.55 (d, 1), 7.9 (s, 1), 8.02 (d, 1), 8.15 (s, 1) ppm.

Aufarbeitung

  1. extractionExtraction with ethyl acetate
  2. washwashing with brine
  3. dry with materialdrying over sodium sulfate and evaporation

Quellen und Nachweise

ORD-Eintrag
ord-ea0eacee9efc4b4fa580d5cb4a1d24ec
Quelldatensatz
uspto-grants-2006_02
Patentnummer
US06995156B2

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