반응 #84642

반응 방정식

tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate

3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid

potassium phosphate

1,4-dioxane water

→

methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid

수율 96.0%

반응 조건

후처리

1. 1
   기타was degassed with nitrogen for 5 min
2. 2
   온도The reaction mixture was cooled to room temperature
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   세척washed with saturated ammonium chloride solution
5. 5
   건조dried with sodium sulfate
6. 6
   기타The residue was purified by silica gel column chromatography

실험 절차

A mixture of tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate (100 mg, 0.25 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (82 mg, 0.29 mmol), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (9 mg, 0.01 mmol) and potassium phosphate (157 mg, 0.74 mmol) in 1,4-dioxane/water (2.5 mL/0.25 mL) was degassed with nitrogen for 5 min and stirred at 100° C. for 30 min under microwave. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with saturated ammonium chloride solution and dried with sodium sulfate. The residue was purified by silica gel column chromatography to afford methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid (114 mg, 96%). MS (ES+) C26H30N4O5 requires: 478, found: 479 [M+H]+.

출처