Methanesulfonic Acid → 5-(5-Methoxycarbonylbenzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74243

반응식

HRID 74243 반응식
Cl.[CH3:2][C:3]1[N:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:6]2[CH:14]=[CH:15][C:16]([C:18]([OH:20])=O)=[CH:17][C:5]=2[N:4]=1.S(Cl)(Cl)=O.[NH2:25][C:26]1[CH:31]=[C:30]([C:32]([O:34][CH3:35])=[O:33])[CH:29]=[CH:28][C:27]=1O.C(N(CC)CC)C.CS(O)(=O)=O.C(=O)([O-])O.[Na+]>O.O1CCCC1>[CH3:35][O:34][C:32]([C:30]1[CH:29]=[CH:28][C:27]2[O:20][C:18]([C:16]3[CH:15]=[CH:14][C:6]4[N:7]([CH:8]5[CH2:9][CH2:10][O:11][CH2:12][CH2:13]5)[C:3]([CH3:2])=[N:4][C:5]=4[CH:17]=3)=[N:25][C:26]=2[CH:31]=1)=[O:33]

참가 물질

9

반응물 6

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 10815Methyl 3-amino-4-hydroxybenzoateHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 674984452-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt

생성물 1

HCID 674986775-(5-Methoxycarbonylbenzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazole수율 15.4%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To 2-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt (see Working Example 4-3) (182 mg, 0.612 mmol) was added thionyl chloride (2 mL), and this was stirred at reflux for 3 hours. After the reaction was complete, concentration at reduced pressure gave a residue that was added to 2-amino-4-methoxycarbonylphenol (117 mg, 0.612 mmol), triethylamine (309 mg, 3.06 mmol) and tetrahydrofuran (5 mL), and this was stirred at room temperature for 14 hours. After the reaction was complete, this was concentrated, and to a dioxane (5 mL) solution of the residue obtained was added methanesulfonic acid (353 mg, 1.46 mmol), and this was heated to reflux for 18 hours. After the reaction solution was cooled, water and saturated aqueous sodium hydrogen carbonate solution were added, and this was extracted with chloroform. After the organic layer obtained was dried over anhydrous sodium sulfate, it was filtered and concentrated. The residue obtained was purified by silica gel column chromatography to yield the title compound (37 mg, 15% yield).

후처리

  1. temperatureat reflux for 3 hours
  2. concentrationconcentration at reduced pressure
  3. customgave a residue that
  4. stirringthis was stirred at room temperature for 14 hours
  5. concentrationthis was concentrated
  6. customto a dioxane (5 mL) solution of the residue obtained
  7. temperaturethis was heated
  8. temperatureto reflux for 18 hours
  9. temperatureAfter the reaction solution was cooled
  10. extractionthis was extracted with chloroform
  11. customAfter the organic layer obtained
  12. dry with materialwas dried over anhydrous sodium sulfate, it
  13. filtrationwas filtered
  14. concentrationconcentrated
  15. customThe residue obtained
  16. customwas purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-242afc8b67574d1680f980ce0cddcfaa
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829035B2

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