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

HRID 348099ノート

反応式

HRID 348099 の反応式
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]

参加物

5

反応物 3

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

生成物 1

HCID 221847702-Carboxy-7-chloro-4-methylthioquinoline収率 76.5%

試薬・触媒・溶媒 1

HCID 21881883Oxolane--water (1/1)溶媒

実験手順

To a solution of 2-carboxy-7-chloro-4-mercaptoquinoline HCl salt (75 mg, 0.31 mmol) in DMF (3 mL) was added Mel (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 CH2Cl2afforded 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;

後処理

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

出典と根拠

ORDレコード
ord-5fe8a0c9ff1a4205b89581b30cbf5a29
出典データセット
uspto-grants-2007_02
特許番号
US07176207B2

反応ノート

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