Dimethylformamide → 1-{[2-(Hex-5-enyl-methyl-carbamoyl)-4-hydroxy-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 1445408Notes

Reaction equation

HRID 1445408 reaction equation
C([N:4]([CH:7](C)C)[CH2:5][CH3:6])(C)C.[CH2:10]([O:12][C:13]([C:15]1([NH:20][C:21]([CH:23]2[CH2:27][CH:26]([OH:28])[CH2:25][CH:24]2[C:29]([OH:31])=O)=[O:22])[CH2:17][CH:16]1[CH:18]=[CH2:19])=[O:14])[CH3:11].CN(C=O)C.CN(C(ON1N=N[C:47]2[CH:48]=[CH:49]C=N[C:46]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:10]([O:12][C:13]([C:15]1([NH:20][C:21]([CH:23]2[CH2:27][CH:26]([OH:28])[CH2:25][CH:24]2[C:29](=[O:31])[N:4]([CH2:5][CH2:6][CH2:49][CH2:48][CH:47]=[CH2:46])[CH3:7])=[O:22])[CH2:17][CH:16]1[CH:18]=[CH2:19])=[O:14])[CH3:11]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668702712-(1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-hydroxy-cyclopentane carboxylic acid diisopropylethylamine salt

Product 1

HCID 668706071-{[2-(Hex-5-enyl-methyl-carbamoyl)-4-hydroxy-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude compound 4 (5.5 mmol) was dissolved in DCM (50 ml) and DMF (14 ml) followed by addition of HATU (2.09 g, 5.5 mmol), 5 (678 mg, 6.0 mmol) and DIPEA (3.08 ml, 17.5 mmol) at room temperature. The reaction was stirred at ambient temperature for 1 h. LC/MS analysis showed complete conversion and the reaction mixture was concentrated in vacuo. The residue was re-dissolved in ethyl acetate (100 ml) and the organic layer washed with 0.1 M HCl (aqueous), K2CO3 (aqueous) and brine, dried (MgSO4) and filtered. Evaporation of the solvent in vacuo gave an oil which was purified by flash chromatography (Silica, ethyl acetate/methanol) to afford the target compound 6 (1.65 g, 74%). TLC (Silica): methanol/ethyl acetate 5:95, Rf=0.5; LC/MS (Method A): tR=3.44 min, >95%, m/z (ESI+)=407 (MH+).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was re-dissolved in ethyl acetate (100 ml)
  3. washthe organic layer washed with 0.1 M HCl (aqueous), K2CO3 (aqueous) and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customEvaporation of the solvent in vacuo
  7. customgave an oil which
  8. customwas purified by flash chromatography (Silica, ethyl acetate/methanol)

Sources & evidence

ORD record
ord-5c6064d1b3e641ae87222c4d3e7f7cf8
Source dataset
uspto-grants-2010_02
Patent number
US07666834B2

Reaction notes

Loading…