Dimethylformamide → HCID 69365248, compound

HRID 1797493Notes

Reaction equation

HRID 1797493 reaction equation
[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13](C(O)=O)[CH:14]=2)[C:9](=[O:19])[N:8]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:7]=1[CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:2][CH2:3][CH3:4].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:40])C=CC=CC=1.C([N:52]([CH2:55]C)CC)C.[C:57]1(CO)[C:69]2[CH2:68][C:67]3[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=3)[C:61]=2[CH:60]=[CH:59][CH:58]=1.CN(C)[CH:74]=[O:75]>O>[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH:52][C:55](=[O:40])[O:75][CH2:74][CH:68]3[C:67]4[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=4[C:61]4[C:69]3=[CH:57][CH:58]=[CH:59][CH:60]=4)[CH:14]=2)[C:9](=[O:19])[N:8]([CH2:20][CH:21]([CH3:22])[CH3:23])[C:7]=1[CH2:24][NH:25][C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 523071-FluorenemethanolHCID 199401P,P-Diphenylphosphinic azideHCID 22176086HCID 22176086, compound

Product 1

HCID 69365248HCID 69365248, compoundYield 82.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of 4-butoxy-3-{{(tert-butoxycarbonyl)amino}methyl}-2-isobutyl-1-oxo-1,2-dihydro-6-isoquinolinecarboxylic acid (synthesized according to the method similar to that in Example 76 (1)) (0.45 g, 1 mmol), diphenylphosphoryl azide (0.26 ml, 1.2 mmol) and triethylamine (0.17 ml, 1.2 mmol) in N,N-dimethylformamide, (10 ml) was stirred at room temperature for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in toluene (20 ml) and the mixture was refluxed with stirring for 1 h. To the obtained mixture was added 9H-fluorenylmethanol (0.29 g, 1.5 mmol) and the mixture was refluxed with stirring for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and recrystallized from tetrahydrofuran-diisopropyl ether to give 9H-fluoren-9-ylmethyl 4-butoxy-3-{{(tert-butoxycarbonyl)-amino}methyl}-2-isobutyl-1-oxo-1,2-dihydro-6-isoquinolinylcarbamate (0.53 g, 82.8%) as crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in toluene (20 ml)
  6. temperaturethe mixture was refluxed
  7. stirringwith stirring for 1 h
  8. temperaturethe mixture was refluxed
  9. stirringwith stirring for 1 h
  10. extractionextracted with ethyl acetate
  11. washThe extract was washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography
  15. customrecrystallized from tetrahydrofuran-diisopropyl ether

Sources & evidence

ORD record
ord-00641ac09ca342e2a0d93ca6f274c5a9
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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