C([O:5][C:6](=O)[NH:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][N:14]=2)[CH2:9]1)(C)(C)C.C(O)([C:23](F)([F:25])[F:24])=O.FC(F)C(O)=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>C(Cl)Cl>[Br:19][C:16]1[CH:17]=[CH:18][C:13]([N:10]2[CH2:11][CH2:12][C@@H:8]([NH:7][C:6](=[O:5])[CH:23]([F:25])[F:24])[CH2:9]2)=[N:14][CH:15]=1
Dissolve [(R)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (4.24 g, 12.43 mmol) in CH2Cl2 (10 mL) and add TFA (5 mL). Stir at RT for 1 h. Evaporate the excess reagent. Dissolve the resulting crude material in CH2Cl2 (50 mL) and cool to 0° C. Add difluoroacetic acid (1.78 g, 18.64 mmol), EDCI (3.57 g, 18.64 mmol), HOBt (2.52 g, 18.64 mmol) and Et3N (5.2 mL, 37.3 mmol). Stir the reaction at 0° C. for 30 min and at RT overnight. Dilute with CH2Cl2 (100 mL) and wash with 0.1 M NaOH (2×50 mL) and H2O (100 mL). Dry the solution with Na2SO4, filter, and concentrate. Purify the crude material, eluting with 100% EtOAc to give 1.98 g (50%) of the title compound. MS/ES m/z (79Br) 321.0 [M+H]+.
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