Sodium sulfate decahydrate → (5-amino-3-bromo-7-iodo-5H-chromeno[2,3-b]pyridin-5-yl)methanol

HRID 931557

반응식

HRID 931557 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=O)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([I:17])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[I-].C[S+](C)C.C[C:24](C)([O-:26])C.[Li+].C[Si]([N:33]=[N+]=[N-])(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>CS(C)=O>[NH2:33][C:15]1([CH2:24][OH:26])[C:4]2[C:5](=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=2)[O:8][C:9]2[C:14]1=[CH:13][C:12]([I:17])=[CH:11][CH:10]=2

참가 물질

8

반응물 6

HCID 62649Sodium sulfate decahydrateHCID 75127Trimethylsulfonium iodideHCID 78378AzidotrimethylsilaneHCID 21226445Aluminium lithium hydrideHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 574756483-bromo-7-iodo-5H-chromeno[2,3-b]pyridin-5-one

생성물 1

HCID 67382607(5-amino-3-bromo-7-iodo-5H-chromeno[2,3-b]pyridin-5-yl)methanol수율 40.8%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
0 °C

실험 절차

To a suspension of 3-bromo-7-iodo-5H-chromeno[2,3-b]pyridin-5-one (20.00 g, 49.8 mmol) and trimethylsulfonium iodide (11.17 g, 54.7 mmol) in 250 mL DMSO under nitrogen atmosphere was added lithium tert-butoxide [1N in heptane (54.7 mL, 54.7 mmol)] drop wise over 40 minutes. After stirring for an additional 30 minutes, trimethylsilylazide (13.21 mL, 100 mmol) was added. After stirring for an additional hour, the reaction mixture was concentrated under reduced pressure. The remaining solution was diluted with water. The resulting solid was filtered off and washed with water. The solid was dissolved in 2-MeTHF, dried over MgSO4 and concentrated. The crude residue was dissolved in 200 mL THF, cooled to 0° C. and treated with LAH (1.888 g, 49.8 mmol). After stirring for 30 minutes, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional 30 minutes. The reaction mixture was then cooled to 0° C. and quenched with sodium sulfate decahydrate (32.1 g, 100 mmol). The reaction mixture was vigorously stirred for one hour, filtered through a plug of celite and concentrated. Purification of the crude residue by column chromatography [0-80% (95:5 EtOAc/MeOH)/DCM] gave (5-amino-3-bromo-7-iodo-5H-chromeno[2,3-b]pyridin-5-yl)methanol (8.80 g, 20.32 mmol, 40.8% yield).

후처리

  1. stirringAfter stirring for an additional hour
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionThe remaining solution was diluted with water
  4. filtrationThe resulting solid was filtered off
  5. washwashed with water
  6. dissolutionThe solid was dissolved in 2-MeTHF
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. dissolutionThe crude residue was dissolved in 200 mL THF
  10. stirringAfter stirring for 30 minutes
  11. customthe cooling bath was removed
  12. stirringto stir for an additional 30 minutes
  13. temperatureThe reaction mixture was then cooled to 0° C.
  14. stirringThe reaction mixture was vigorously stirred for one hour
  15. filtrationfiltered through a plug of celite and
  16. concentrationconcentrated
  17. customPurification of the crude residue by column chromatography [0-80% (95:5 EtOAc/MeOH)/DCM]

출처 및 근거

ORD 기록
ord-12a189830ed24d84aa9d69c97610fd13
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296759B2

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