Sodium triacetoxyborohydride → 1,1-Dimethylethyl ((3S,4R)-3-hydroxy-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-4-piperidinyl)carbamate

HRID 657030노트

반응식

HRID 657030 반응식
CO[CH:3](O)[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[CH:8]=[CH:7][C:6]1=[O:17].CC([N:23]([C@@H:27]1[CH2:32][CH2:31][NH:30][CH2:29][C@@H:28]1[OH:33])[C:24](=[O:26])[O-:25])(C)C.OCC[CH2:37][C:38]1[C:43](=O)N(CC2C=CC(OC)=CC=2)NC(=O)[CH:39]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[OH:33][C@@H:28]1[C@H:27]([NH:23][C:24](=[O:26])[O:25][C:38]([CH3:43])([CH3:39])[CH3:37])[CH2:32][CH2:31][N:30]([CH2:3][CH2:4][N:5]2[C:14]3[C:9](=[N:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=3)[CH:8]=[CH:7][C:6]2=[O:17])[CH2:29]1

참가 물질

7

반응물 4

HCID 5049666Sodium triacetoxyborohydrideHCID 675265645-(3-Hydroxypropyl)-1-{[4-(methyloxy)phenyl]methyl}-1,2-dihydro-3,6-pyridazinedioneHCID 86635329[7-(methoxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]acetaldehyde methyl hemiacetalHCID 866353341,1-dimethylethyl[(3S,4R)-3-hydroxy-4-piperidinyl]carbamate

생성물 1

HCID 585793851,1-Dimethylethyl ((3S,4R)-3-hydroxy-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-4-piperidinyl)carbamate

시약·촉매·용매 2

HCID 887Methanol용매HCID 6212Chloroform용매

실험 절차

[7-(methoxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]acetaldehyde methyl hemiacetal (200 mg) and 1,1-dimethylethyl[(3S,4R)-3-hydroxy-4-piperidinyl]carbamate (for a synthesis see WO2004058144, Example 5(c), cis-(3-hydroxy-piperidin-4-yl)-carbamic acid tert-butyl ester Enantiomer 2) (182 mg) were stirred in chloroform (10 ml) plus MeOH (0.5 ml) under argon for 2 h. Sodium triacetoxyborohydride (534 mg) was added in one portion and the mixture was stirred at rt overnight, then quenched by addition of saturated aqueous sodium hydrogen cabonate (2 ml). The organic phase was separated using a hydrophobic frit and the aqueous phase was extracted with DCM (2×20 ml). The organic extracts were combined, dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure to give the crude product, which was purified by column chromatography on silica, eluted with 0-20% (2M ammonia in MeOH) in DCM. Appropriate fractions were combined and evaporated under reduced pressure to give the title compound (226 mg) as an off-white foam.

후처리

  1. customquenched by addition of saturated aqueous sodium hydrogen cabonate (2 ml)
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with DCM (2×20 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto give the crude product, which
  8. customwas purified by column chromatography on silica
  9. washeluted with 0-20% (2M ammonia in MeOH) in DCM
  10. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-75413877429d4323a4ccab5fb04d673c
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071592B2

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