Potassium Carbonate → methyl 3-(4-{5-[(pyridin-3-ylmethylamino)carbonyl]-1H-benzimidazol-1-yl}phenoxy)cyclobutanecarboxylate

HRID 2111804ノート

反応式

HRID 2111804 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]([NH:19][CH2:20][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)=[O:18])=[CH:16][C:11]=3[N:10]=[CH:9]2)=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O[CH:62]2[CH2:65][CH:64]([C:66]([O:68][CH3:69])=[O:67])[CH2:63]2)(=O)=O)=CC=1>CN(C=O)C>[N:23]1[CH:24]=[CH:25][CH:26]=[C:21]([CH2:20][NH:19][C:17]([C:15]2[CH:14]=[CH:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([O:1][CH:62]5[CH2:65][CH:64]([C:66]([O:68][CH3:69])=[O:67])[CH2:63]5)=[CH:3][CH:4]=4)[CH:9]=[N:10][C:11]=3[CH:16]=2)=[O:18])[CH:22]=1

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 12815113Methyl 3-{[(4-methylbenzene)sulfonyl]oxy}cyclobutane-1-carboxylateHCID 690682371-(4-Hydroxyphenyl)-N-(pyridin-3-ylmethyl)-1H-benzimidazole-5-carboxamide

生成物 1

HCID 69063376methyl 3-(4-{5-[(pyridin-3-ylmethylamino)carbonyl]-1H-benzimidazol-1-yl}phenoxy)cyclobutanecarboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

Methyl 3-hydroxycyclobutanecarboxylate (671 mg, 5.16 mmol) was dissolved in CH2Cl2 (20 mL). Pyridine (0.63 mL, 7.73 mmol) was then added followed by p-toluenesulfonic anhydride (1.85 g, 5.67 mmol) and the reaction was stirred at rt for 14 h. The reaction was concentrated in vacuo, dissolved in ether, and washed with H2O, 2M HCl, 2M NaHCO3, brine, and dried over MgSO4. The solution was then filtered, and concentrated in vacuo to give methyl 3-{[(4-methylphenyl)sulfonyl]oxy}cyclobutanecarboxylate as a colorless oil, which was taken on crude. 1-(4-Hydroxyphenyl)-N-(pyridin-3-ylmethyl)-1H-benzimidazole-5-carboxamide (0.88 g, 2.56 mmol), 18-crown-6 (1.36 g, 5.13 mmol), and K2CO3 (0.71 g, 5.13 mmol) were dissolved in DMF (26 mL) in a 50 mL round bottom flask. The reaction was heated to 80° C. under N2 atmosphere upon which methyl 3-{[(4-methylphenyl)sulfonyl]oxy}cyclobutanecarboxylate was added drop-wise. After heating at 80° C. for 48 h, the reaction was cooled to rt, concentrated in vacuo, and purified using silica gel chromatography (5% methanol:CH2Cl2). To remove residual p-toluenesulfonic acid and 18-crown-6, the foamy white solid was washed with ethyl acetate. The combined organic washes were then washed with water and dried over MgSO4, filtered, and concentrated in vacuo to provide methyl 3-(4-{5-[(pyridin-3-ylmethylamino)carbonyl]-1H-benzimidazol-1-yl}phenoxy)cyclobutanecarboxylate as an off-white foamy solid (3:1 trans:cis isomers). MS (ES+): m/z 457 (100) [MH+].

後処理

  1. additionwas added drop-wise
  2. temperaturethe reaction was cooled to rt
  3. concentrationconcentrated in vacuo
  4. custompurified
  5. customTo remove residual p-toluenesulfonic acid and 18-crown-6
  6. washthe foamy white solid was washed with ethyl acetate
  7. washThe combined organic washes were then washed with water
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-c2e15770a1a742648cf06476ec9c39b8
出典データセット
uspto-grants-2009_04
特許番号
US07521448B2

反応ノート

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