Triethylamine → HCID 60206227, compound

HRID 1797696Notes

Reaction equation

HRID 1797696 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[N:11]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:12](=[O:34])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:17][C:16]([C:26]1[S:27][CH:28]=[C:29](C(O)=O)[N:30]=1)=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])C=CC=CC=1.C([N:58]([CH2:61]C)CC)C.[CH:63]1[C:75]2[CH:74]([CH2:76][OH:77])[C:73]3[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=3)[C:67]=2[CH:66]=[CH:65][CH:64]=1>CN(C)C=O.O>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[N:11]([CH2:35][CH:36]([CH3:37])[CH3:38])[C:12](=[O:34])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:17][C:16]([C:26]1[S:27][CH:28]=[C:29]([NH:58][C:61](=[O:46])[O:77][CH2:76][CH:74]3[C:75]4[CH:63]=[CH:64][CH:65]=[CH:66][C:67]=4[C:68]4[C:73]3=[CH:72][CH:71]=[CH:70][CH:69]=4)[N:30]=1)=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 904669H-Fluorene-9-methanolHCID 199401P,P-Diphenylphosphinic azideHCID 22175971HCID 22175971, compound

Product 1

HCID 60206227HCID 60206227, compoundYield 51.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinyl)-1,3-thiazole-4-carboxylic acid (1.60 g, 3 mmol), diphenylphosphoryl azide (0.78 ml, 3.6 mmol) and triethylamine (0.50 ml, 3.6 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 refluxed for 1 h. To the resulting mixture was added 9-fluorenylmethanol (0.88 g, 4.5 mmol), and the mixture was stirred at 100° C. for 3 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 to give 9H-fluoren-9-ylmethyl 2-(3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinyl)-1,3-thiazol-4-ylcarbamate (1.12 g, 51.4%) as an amorphous solid.

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. temperaturerefluxed for 1 h
  7. extractionextracted with ethyl acetate
  8. washThe extract was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-12dfaad7bfd54b7694cf1ba37b3ba303
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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