Water → N-({(1S,2S,5R)-3-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]-3-azabicyclo[3.1.0]hex-2-yl}methyl)-1,3-benzoxazol-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-5 (0.095 g, 0.30 mmol) in CH2Cl2 (1 mL) at ambient temperature was added triethylamine (0.15 g, 1.5 mmol) and methanesulfonyl chloride (0.052 g, 0.45 mmol) and the reaction was stirred for 0.5 hours. The reaction was quenched with water (5 mL) and the reaction was extracted with CH2Cl2 (10 mL). The organic phase was dried over magnesium sulfate and concentrated to afford an oil which was used without further purification. The residue was redissolved in DMF (1 mL) and to this solution was added sodium azide (0.20 g, 3.0 mmol) and the reaction was heated to 60° C. for 1 h. The reaction was cooled and diluted with EtOAc (15 mL). The organic phase was washed with water (3×10 mL), dried over magnesium sulfate and concentrated to an oil which was used without further purification. The residue was redissolved in THF (3 mL) at ambient temperature and to the solution was added polymer-bound triphenylphosphine (0.41 g, 0.91 mmol; 2.2 mmol/g loading) and water (0.11 g, 6.0 mmol). The reaction was stirred for 12 hours and quenched with magnesium sulfate. The reaction was filtered to yield a foamy solid of >90% purity. ESI+ MS: [M+H]+ 314.3. The foamy solid was resuspended in DMF (1 mL) at ambient temperature was added triethylamine (0.058 g, 0.57 mmol) and 2-chlorobenzoxazole (0.041 g, 0.27 mmol) and the reaction was heated for 3 hours at 65° C. The reaction was cooled and quenched with water (10 mL) and diluted with EtOAc (20 mL). The organic phases were washed with water (3×10 mL) and dried over magnesium sulfate. The residue was purified by normal phase silica gel chromatography (0 to 100% EtOAc in hexanes, then 0 to 20% MeOH in EtOAc) to afford the product as a foamy, off-white solid. HRMS [M+H] C24H22N4O2S1 calc'd 431.1536, found 431.1527.

Provenance & Evidence