Diisopropylethylamine → N-[5-((4aR*,8aS*)-2-amino-4,4a,5,6-tetrahydro-7-oxa-3-thia-1-azanaphthalen-8a-yl)thiophen-3-yl]-5-cyanopyridine-2-carboxamide

HRID 218010

Reaktionsgleichung

Reaktionsgleichung von HRID 218010
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(OC([N:61]([C:69]1[S:78][CH2:77][C@H:76]2[C@@:71]([C:79]3[S:80][CH:81]=[C:82]([NH2:84])[CH:83]=3)([CH2:72][O:73][CH2:74][CH2:75]2)[N:70]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C>[NH2:61][C:69]1[S:78][CH2:77][C@H:76]2[C@@:71]([C:79]3[S:80][CH:81]=[C:82]([NH:84][C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=4)=[O:11])[CH:83]=3)([CH2:72][O:73][CH2:74][CH2:75]2)[N:70]=1

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2724699PyBOPHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 67216640(+)-N,N-di(tert-butyloxycarbonyl)-[(4aR*,8aS*)-8a-(4-aminothiophen-2-yl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine

Produkt 1

HCID 68587014N-[5-((4aR*,8aS*)-2-amino-4,4a,5,6-tetrahydro-7-oxa-3-thia-1-azanaphthalen-8a-yl)thiophen-3-yl]-5-cyanopyridine-2-carboxamideAusbeute 79,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

5-Cyanopyridine-2-carboxylic acid (19.0 mg), diisopropylethylamine (50.7 μl) and PyBOP (83.5 mg) were sequentially added to a solution of (+)-N,N-di(tert-butyloxycarbonyl)-[(4aR*,8aS*)-8a-(4-aminothiophen-2-yl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine (50 mg) in dichloromethane (5.0 ml) in an ice bath. The mixture was returned to room temperature and stirred overnight. The solvent was evaporated under reduced pressure and the residue was purified by NH-silica gel column chromatography. The resulting intermediate was dissolved in dichloromethane (4.0 ml) and TFA (1.0 ml) was added. After stirring at room temperature for four hours, ice was added to terminate the reaction. The mixture was neutralized with a sodium bicarbonate solution, and the aqueous layer was neutralized with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH-silica gel column chromatography to obtain the title compound (33.9 mg).

Aufarbeitung

  1. customwas returned to room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was purified by NH-silica gel column chromatography
  4. dissolutionThe resulting intermediate was dissolved in dichloromethane (4.0 ml)
  5. additionTFA (1.0 ml) was added
  6. stirringAfter stirring at room temperature for four hours
  7. additionice was added
  8. customto terminate
  9. customthe reaction
  10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by NH-silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e34d0370d3c84c9099fbc5c7b204520a
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198269B2

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