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

HRID 570118Notes

Reaction equation

HRID 570118 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 EtOAc (100 mL) and the organic phase washed with 0.1 M HCl (aq), K2CO3 (aq) and brine, dried (MgSO4) and filtered. Evaporation of the solvent in vacuo gave an oil which was purified by flash chromatography (Silica, EtOAc:MeOH) to afford the target compound 6 (1.65 g, 74%). TLC (Silica): MeOH:EtOAc 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 EtOAc (100 mL)
  3. washthe organic phase washed with 0.1 M HCl (aq), K2CO3 (aq) 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, EtOAc:MeOH)

Sources & evidence

ORD record
ord-9fc210917e2143a9a776dcec98a650a4
Source dataset
uspto-grants-2015_05
Patent number
US09023808B2

Reaction notes

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