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

Reaction equation

HRID 218010 reaction equation
[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

Participants

8

Reactant 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

Product 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-carboxamideYield 79.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e34d0370d3c84c9099fbc5c7b204520a
Source dataset
uspto-grants-2012_06
Patent number
US08198269B2

Linked notes

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