Dimethylacetamide → Carbamic acid, N-[(1R,2S)-1-[[(cyclopropylsulfonyl)amino]carbonyl]-2-ethenylcyclopropyl]-, 1,1-dimethylethyl ester

HRID 1877322Notes

Reaction equation

HRID 1877322 reaction equation
C([C@:8]1([C:14]([OH:16])=O)[CH2:10][C@:9]1(N)[CH:11]=[CH2:12])(OC(C)(C)C)=O.[C:17]([C:24]1NC=CN=1)([C:19]1NC=CN=1)=[O:18].[CH:29]1([S:32]([NH2:35])(=[O:34])=[O:33])[CH2:31][CH2:30]1.[CH:36](N(C(C)C)CC)(C)C.C1CCN2C(=NCCC2)CC1.C[N:57](C)[C:58](=[O:60])C>>[C:17]([O:18][C:58](=[O:60])[NH:57][C@:8]1([C:14](=[O:16])[NH:35][S:32]([CH:29]2[CH2:31][CH2:30]2)(=[O:34])=[O:33])[CH2:10][C@H:9]1[CH:11]=[CH2:12])([CH3:19])([CH3:24])[CH3:36]

Participants

7

Reactant 6

HCID 31374DimethylacetamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 15765418CyclopropanesulfonamideHCID 68613219HCID 68613219, compound

Product 1

HCID 45480526Carbamic acid, N-[(1R,2S)-1-[[(cyclopropylsulfonyl)amino]carbonyl]-2-ethenylcyclopropyl]-, 1,1-dimethylethyl ester

Procedure

To a stirring solution of 500 mg (1R,2S)-1-BOC-amino-2-vinylcyclopropane carboxylic acid (2.2 mmol) in 4 mL of DMA (N,N-dimethylacetamide), was added 370 mg of carbonyl diimidazole (CDI, 2.3 mmol). The reaction mixture was stirred at RT for 1 hr, followed by addition of 280 mg of cyclopropylsulfonamide (2.3 mmol), 1 mL of diisopropylethylamine and 350 uL of DBU. The resulting mixture was stirred at 60° C. overnight. The solvent was removed, and normal workup was applied with 100 mL of EtOAc, washed with 10 mL of 1.0 N aqueous HCl, dried over anhydrous Na2SO4. After concentration, the residue was purified by flash column chromatography giving 580 mg of white solid. 1HNMR (CDCl3, 400 MHz) δ 9.7 (br s, 1H), 5.61 (m, 1H), 5.33 (br dd, 2H, J=9.6, 1.2 Hz), 5.18 (dd, J=9.6, 1.2 Hz), 2.92 (m, 1H) 2.14 (q, 1H, J=8.0 Hz), 1.91 dd, 1H, J=8.4, 2.4 Hz), 1.55 (br s, 2H), 1.47 (s, 9H), 1.40 (m, 2H), 1.30 (m, 2H), 0.95-1.15 (m, 2H). LC/MS: m/z 329.1, (M−1, ES−).

Workup

  1. stirringThe resulting mixture was stirred at 60° C. overnight
  2. customThe solvent was removed
  3. washwashed with 10 mL of 1.0 N aqueous HCl
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationAfter concentration
  6. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b8a8f41af22a46cc844166cfaca25043
Source dataset
uspto-grants-2012_11
Patent number
US08309685B2

Reaction notes

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