1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(1-Cyclopropanesulfonylaminocarbonyl-2-vinyl-cyclopropyl)-2-(hex-5-enyl-methyl-amino-carbonyl)-4-hydroxy-cyclopentane-carboxamide

HRID 390124Notes

Reaction equation

HRID 390124 reaction equation
[CH2:1]([N:7]([CH3:27])[C:8]([CH:10]1[CH2:14][CH:13]([OH:15])[CH2:12][CH:11]1[C:16]([NH:18][C:19]1([C:24](O)=[O:25])[CH2:21][CH:20]1[CH:22]=[CH2:23])=[O:17])=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].CCN=C=NCCCN(C)C.[CH:39]1([S:42]([NH2:45])(=[O:44])=[O:43])[CH2:41][CH2:40]1.C1CCN2C(=NCCC2)CC1>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH:39]1([S:42]([NH:45][C:24]([C:19]2([NH:18][C:16]([CH:11]3[CH2:12][CH:13]([OH:15])[CH2:14][CH:10]3[C:8]([N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6])[CH3:27])=[O:9])=[O:17])[CH2:21][CH:20]2[CH:22]=[CH2:23])=[O:25])(=[O:44])=[O:43])[CH2:41][CH2:40]1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 668702741-{[2-(Hex-5-enylmethylcarbamoyl)-4-hydroxycyclopentanecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid

Product 1

HCID 68589808N-(1-Cyclopropanesulfonylaminocarbonyl-2-vinyl-cyclopropyl)-2-(hex-5-enyl-methyl-amino-carbonyl)-4-hydroxy-cyclopentane-carboxamideYield 77%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

The crude acid 20a (410 mg, 1.09 mmol) was dissolved in DMF (1.5 ml) and DCM (4.5 ml) followed by addition of EDAC (417 mg, 2.18 mmol) at room temperature. The mixture was allowed to incubate with stirring at room temperature. After 10 min, DMAP (133 mg, 1.09 mmol) was added followed by another 20 min incubation at room temperature. Subsequently, a pre-mixed solution of cyclopropanesulfonic acid amide (527 mg, 4.36 mmol) and DBU (663 mg, 4.36 mmol) in DMF (2 ml) and DCM (2 ml) was added followed by heating in the microwave to 100° C. for 30 min. The resulting red solution was concentrated in vacuo and re-dissolved in EtOAc (20 ml). The organic phase was washed with 1 M HCl (aq) (3×10 ml) and brine (10 ml), dried (MgSO4) and filtered. The solvent was evaporated in vacuo to yield the crude sulfonamide which was further purified by chromatography (Silica, EtOAc/MeOH, 97.5:2.5) to afford the title compound (403 mg, 77%); LC/MS, >95%, m/z (ESI+)=482(MH+)

Workup

  1. waitfollowed by another 20 min
  2. customat room temperature
  3. temperatureby heating in the microwave to 100° C. for 30 min
  4. concentrationThe resulting red solution was concentrated in vacuo
  5. dissolutionre-dissolved in EtOAc (20 ml)
  6. washThe organic phase was washed with 1 M HCl (aq) (3×10 ml) and brine (10 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customThe solvent was evaporated in vacuo
  10. customto yield the crude sulfonamide which
  11. customwas further purified by chromatography (Silica, EtOAc/MeOH, 97.5:2.5)

Sources & evidence

ORD record
ord-e9fc22f7b1d343fd84341cb71655fe2d
Source dataset
uspto-grants-2013_02
Patent number
US08383584B2

Reaction notes

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