Ammonium Chloride → HCID 11950324, 화합물

HRID 549234노트

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HRID 549234 반응식
[CH3:1][C:2]1[N:3]([CH2:30][CH2:31][CH3:32])[N:4]=[C:5]2[C:14]=1[C:13]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:7]=[C:6]2[N:15](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O.C([Li])(C)(C)C.[O:38]1[CH2:43][CH2:42][C:41](=[O:44])[CH2:40][CH2:39]1.[Cl-].[NH4+]>O1CCCC1.CCCCC>[NH2:15][C:6]1[C:5]2=[N:4][N:3]([CH2:30][CH2:31][CH3:32])[C:2]([CH2:1][C:41]3([OH:44])[CH2:42][CH2:43][O:38][CH2:39][CH2:40]3)=[C:14]2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 67157595HCID 67157595, 화합물HCID 178418306HCID 178418306, 화합물

생성물 1

HCID 11950324HCID 11950324, 화합물수율 42.1%

시약·촉매·용매 2

HCID 8003Pentane용매HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

A solution of di(tert-butyl) 1-methyl-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate (1.32 g, 3.00 mmol) in anhydrous tetrahydrofuran (THF) (30 mL) was cooled to −78° C. under an argon atmosphere. tert-Butyllithium (4.4 mL of a 1.7 M solution in pentane) was added over a period of five minutes, and the resulting dark-colored solution was stirred at −78° C. for 30 minutes. Tetrahydro-4H-pyran-4-one (901 mg, 9.0 mmol) was added, and reaction mixture was stirred for 10 minutes. The −78° C. bath was replaced with a 0° C. bath, and then saturated aqueous ammonium chloride (30 mL) was added. The aqueous layer was separated and extracted three times with tert-butyl methyl ether, and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.3 g) was purified by automated flash chromatography (eluting with ethyl acetate) and heated in refluxing 1 M hydrogen chloride in ethanol (50 mL) for one hour. The solution was allowed to cool to room temperature and then made basic with the addition of 2 M aqueous sodium carbonate. The resulting solution was extracted four times with chloroform, and the combined extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.2 g) was purified by automated flash chromatography and recrystallized from acetonitrile to provide 430 mg of 4-[(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)methyl]tetrahydro-2H-pyran-4-ol as a white solid, mp 209-211° C.

후처리

  1. customreaction mixture
  2. stirringwas stirred for 10 minutes
  3. customThe −78° C. bath
  4. customwas replaced with a 0° C.
  5. customThe aqueous layer was separated
  6. extractionextracted three times with tert-butyl methyl ether
  7. dry with materialthe combined organic fractions were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue (1.3 g) was purified by automated flash chromatography (eluting with ethyl acetate)
  11. temperatureheated
  12. temperaturein refluxing 1 M hydrogen chloride in ethanol (50 mL) for one hour
  13. temperatureto cool to room temperature
  14. additionmade basic with the addition of 2 M aqueous sodium carbonate
  15. extractionThe resulting solution was extracted four times with chloroform
  16. dry with materialthe combined extracts were dried over magnesium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customThe residue (1.2 g) was purified by automated flash chromatography
  20. customrecrystallized from acetonitrile

출처 및 근거

ORD 기록
ord-b116d843c00245c687bd3b98d794295a
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943636B2

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