2,6-Lutidine → tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}pyridin-3-yl)ethyl]morpholine-4-carboxylate

HRID 629707

Reaktionsgleichung

Reaktionsgleichung von HRID 629707
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20]([OH:22])=O)[CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C(C)=CC=CC=1C.[NH2:55][C:56]1[C:61]([CH2:62][CH2:63][C@H:64]2[O:69][CH2:68][C@@H:67]([CH2:70][O:71][Si:72]([C:75]([CH3:78])([CH3:77])[CH3:76])([CH3:74])[CH3:73])[N:66]([C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80])[CH2:65]2)=[CH:60][CH:59]=[CH:58][N:57]=1>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Si:72]([O:71][CH2:70][C@H:67]1[N:66]([C:79]([O:81][C:82]([CH3:83])([CH3:84])[CH3:85])=[O:80])[CH2:65][C@@H:64]([CH2:63][CH2:62][C:61]2[C:56]([NH:55][C:20](=[O:22])[C@H:6]([CH:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[NH:5][C:3]([O:2][CH3:1])=[O:4])=[N:57][CH:58]=[CH:59][CH:60]=2)[O:69][CH2:68]1)([C:75]([CH3:76])([CH3:77])[CH3:78])([CH3:73])[CH3:74]

Komponenten

8

Edukt 4

HCID 79372,6-LutidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 86726313tert-butyl (2R,5S)-2-[2-(2-aminopyridin-3-yl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

Produkt 1

HCID 86726314tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}pyridin-3-yl)ethyl]morpholine-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

To N-(methoxycarbonyl)-β-phenyl-L-phenylalanine (1.1 eq.) in DMF (0.15 M) at rt were added HATU (1.4 eq.) and 2,6-lutidine (3 eq.). The reaction mixture was stirred for 30 min and tert-butyl (2R,5S)-2-[2-(2-aminopyridin-3-yl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate (1 eq) was added. The reaction mixture was stirred at 60° C. for 16 h and diluted with EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by automated SiO2 flash chromatography system using solvent gradient of 0% to 10% MeOH/CH2Cl2 to afford the desired compound. Alternatively, DMF could be replaced as solvent by pyridine to ease coupling involving less reactive amine.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at 60° C. for 16 h
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by automated SiO2 flash chromatography system

Quellen und Nachweise

ORD-Eintrag
ord-b2b957dacb19467d8520ec3ed9080c93
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315475B2

Verknüpfte Notizen

Wird geladen…