Acetic Acid → HCID 86648789, 화합물

HRID 43855노트

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HRID 43855 반응식
[CH2:1]([NH2:4])[CH2:2][CH3:3].[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][CH:16]2[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:17]2=O)=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12].C(O)(=O)C.C([BH3-])#N.[Na+]>O1CCCC1.CO>[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][C@@H:16]2[CH2:21][CH2:20][NH:19][CH2:18][C@H:17]2[NH:4][CH2:1][CH2:2][CH3:3])=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12].[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][NH:19][CH2:18][C@H:17]2[NH:4][CH2:1][CH2:2][CH3:3])=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 7852PropylamineHCID 5003444Sodium cyanoborohydrideHCID 68406285tert-Butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate

생성물 1

HCID 86648789HCID 86648789, 화합물수율 12%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

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온도
70 °C

실험 절차

Propylamine (226 μL, 2.75 mmol) was added to a mixed solution of tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (102 mg, 0.275 mmol) in tetrahydrofuran (5 mL) and methanol (5 mL) under ice-cooling, and the mixture was heated under reflux at 70° C. for three hours. The reaction solution was concentrated under reduced pressure, and then the residue was dissolved in tetrahydrofuran (5 mL) and methanol (5 mL). Acetic acid (315 μL, 5.50 mmol) and sodium cyanoborohydride (69 mg, 1.10 mmol) were added, and the mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, and a 1 N aqueous hydrochloric acid solution was added. The aqueous layer was washed with diethyl ether. The aqueous layer was concentrated under reduced pressure with heating, and then saturated aqueous sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by NH-silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v) to obtain 17 mg of the cis isomer of the title compound (20%) as a colorless oily substance and 10.0 mg of the trans isomer of the title compound (12%) as a colorless oily substance.

후처리

  1. temperaturecooling
  2. temperaturethe mixture was heated
  3. concentrationThe reaction solution was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in tetrahydrofuran (5 mL)
  5. concentrationThe reaction solution was concentrated under reduced pressure
  6. additiona 1 N aqueous hydrochloric acid solution was added
  7. washThe aqueous layer was washed with diethyl ether
  8. concentrationThe aqueous layer was concentrated under reduced pressure
  9. temperaturewith heating
  10. additionsaturated aqueous sodium bicarbonate solution was added to the residue
  11. extractionfollowed by extraction with chloroform
  12. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  13. customthe insoluble matter was separated by filtration
  14. concentrationThe filtrate was concentrated under reduced pressure
  15. customthe resulting residue was purified by NH-silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v)

출처 및 근거

ORD 기록
ord-52a889c85f4148e8948d5b266f061dfc
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536197B2

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