Methylamine → HCID 86592069, compound

HRID 1797492Notes

Reaction equation

HRID 1797492 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)C=CC=CC=1.C([N:52]([CH2:55]C)CC)C.C[NH2:58].[O:59]1[CH2:63]CCC1>CN(C)C=O.O>[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH:58][C:63]([NH:52][CH3:55])=[O:59])[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:27])[O:28][C:29]([CH3:32])([CH3:30])[CH3:31])[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22176086HCID 22176086, compound

Product 1

HCID 86592069HCID 86592069, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

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 a solution of 2N methylamine in tetrahydrofuran (1 ml, 2 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 recrystallized from tetrahydrofuran-diisopropyl ether to give tert-butyl {4-butoxy-2-isobutyl-6-{{(methylamino)carbony}-amino}-1-oxo-1,2-dihydro-3-isoquinolinyl}methylcarbamate (0.39 g, 83.0%) as an amorphous.

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 recrystallized from tetrahydrofuran-diisopropyl ether

Sources & evidence

ORD record
ord-d9f53fb79441472aa6fb4ffbe014fb43
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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