1,2-Dichloroethane → HCID 59547322, compound

Participants

Reaction Steps

(3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide (20 mg, 87 μmol, 1.4 eq.), EDC (17 mg, 87 μmol, 1.4 eq.) and HOBt (13 mg, 87 μmol, 1.4 eq.) were combined in DMF (0.3 mL) and stirred at room temp. for 0.5 hrs. (5S,8S)-7-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-2-oxo-3-phenyl-1-oxa-3,7-diazaspiro[4.4]nonane-8-carboxylic acid (H1) (31 mg 62 μmol, 1 eq.) and DIEA (33 μL, 186 mol, 3 eq.) were added to the mixture and stirred at room temp. overnight. 1.0 M histamine (aq., 31 μL, 0.5 eq.) was added and the resulting mixture was stirred for 0.5 hrs. Ethyl acetate was added and the mixture was washed first with 1N HCl then with 1M K2CO3; and then extracted with ethyl acetate. The combined organic layers concentrated and chromatography using DCM and 20% MeOH in DCM gave 20 mg (30 μmol) of (5S,8S)-7-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)-2-oxo-3-phenyl-1-oxa-3,7-diazaspiro[4.4]nonane-8-carboxamide (I1). LC MS+/−: 668.56/666.64 at 3.24 min (10-90%, 3-5 min, Formic Acid).

Provenance & Evidence