Acetonitrile → HCID 54140032, 화합물

HRID 2412439노트

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HRID 2412439 반응식
[C:1](#[N:3])[CH3:2].O1CCCC1.C([Li])CCC.[CH:14]([N:17]1[C:21]2[CH:22]=[C:23]([C:26](=O)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[NH2:34])([CH3:16])[CH3:15]>C(OCC)(=O)C.O>[CH:14]([N:17]1[C:21]2[CH:22]=[C:23]([C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:2][C:1]#[N:3])[CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[NH2:34])([CH3:16])[CH3:15]

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 8028Tetrahydrofuran2회HCID 20432643HCID 20432643, 화합물HCID 178418339Butyllithium

생성물 1

HCID 54140032HCID 54140032, 화합물

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

Forty millimoles (2.1 ml.) of dry acetonitrile were added to 30 ml. of tetrahydrofuran. A nitrogen blanket was applied and the temperature of the solution lowered to about -78° C. by means of an external acetone/dry ice bath. Twenty-five milliliters of a 1.6M solution of n-butyl lithium were added. After stirring at -78° C. for 30 minutes, a solution of 2.8 g. (10 mmoles) of 1-isopropyl-2-amino-6-benzoylbenzimidazole in 30 ml. of tetrahydrofuran was added. The reaction solution was allowed to warm to about -20° C. and was then stirred for 5 hours at -20° to -5° C. Water and ethyl acetate were then added and the layers were separated. The organic layer was dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was dissolved in 100 ml. of 98% formic acid. After stirring on a hot water bath for 2.5 hours, the solution was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and washed with a saturated solution of sodium bicarbonate. The organic solution was dried over magnesium sulfate, filtered, and evaporated. The residue was chromatographed over silica gel, eluting first with ethyl acetate to remove non-polar impurities, then with 10% methanol/90% ethyl acetate to elute the title product. The product was further purified by reverse phase chromatography, eluting with 60% aqueous methanol, followed by crystallization from methyl ethyl ketone, resulting in 350 mg. of the title product, M+ =302.

후처리

  1. customthe temperature of the solution lowered to about -78° C. by means of an external acetone/dry ice bath
  2. temperatureto warm to about -20° C.
  3. stirringwas then stirred for 5 hours at -20° to -5° C
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. dissolutionThe residue was dissolved in 100 ml
  9. stirringAfter stirring on a hot water bath for 2.5 hours
  10. customthe solution was evaporated under reduced pressure
  11. dissolutionThe residue was dissolved in ethyl acetate
  12. washwashed with a saturated solution of sodium bicarbonate
  13. dry with materialThe organic solution was dried over magnesium sulfate
  14. filtrationfiltered
  15. customevaporated
  16. customThe residue was chromatographed over silica gel
  17. washeluting first with ethyl acetate
  18. customto remove non-polar impurities
  19. washwith 10% methanol/90% ethyl acetate to elute the title product
  20. customThe product was further purified by reverse phase chromatography
  21. washeluting with 60% aqueous methanol
  22. customfollowed by crystallization from methyl ethyl ketone
  23. customresulting in 350 mg

출처 및 근거

ORD 기록
ord-d4ca6bf66e224ed3a5453fd9f29d7c06
출처 데이터셋
uspto-grants-1985_01
특허 번호
US04492708

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