반응 #49251

반응 방정식

compounds

(2R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-hydroxy-4-phenylpyrrolidine-1-carboxylate

(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-(oxazol-2-yl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate

3-(dipropylcarbamoyl)-5-(oxazol-2-yl)benzoic acid

HATU

DIEA

→

amide

수율 98.0%

N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide

수율 98.0%

용매

DCM

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction solution was stirred 16 h at rt
2. 2
   기타the reaction solution was partitioned between ethyl acetate and water
3. 3
   농축the organic layer was concentrated
4. 4
   기타the crude product was purified by chromatography
5. 5
   세척eluting with a step gradient of 20% to 50% to 70% ethyl acetate in hexanes

실험 절차

Step 17 (F): (2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-(oxazol-2-yl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate. To a solution of 3-(dipropylcarbamoyl)-5-(oxazol-2-yl)benzoic acid (prepared as reported in WO 2002/02512, 20 mg, 0.062 mmol) in DCM is added HATU (28 mg, 0.073 mmol) and DIEA (33 mg, 0.26 mmol). After the solution is stirred at rt for 5 min, a 28 mg portion of the compounds of step 17 (E) (0.052 mmol) is added. The reaction solution was stirred 16 h at rt, and then the reaction solution was partitioned between ethyl acetate and water, the organic layer was concentrated, and the crude product was purified by chromatography eluting with a step gradient of 20% to 50% to 70% ethyl acetate in hexanes to provide 40 mg (98%) of the desired amide. MS (ESI) (M+H−Boc)+=739.34

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