[S:1]1[C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=[CH:2]1.[Li]CCCC.CN(OC)[C:16](=[O:21])[C:17]([F:20])([F:19])[F:18].[CH:24]1[CH:25]=[CH:26][C:27]2N(O)N=N[C:28]=2[CH:29]=1.C[CH2:35][N:36]=[C:37]=NCCCN(C)C.C(CN)C1C=CC=CC=1>C1COCC1.CN(C=O)C>[CH2:35]([N:36]([CH3:37])[C:6]([C:5]1[S:1][C:2]([C:16](=[O:21])[C:17]([F:18])([F:19])[F:20])=[N:3][CH:4]=1)=[O:8])[C:28]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:29]=1
To a solution (0.2 M) of 1,3-thiazole-5-carboxylic acid (from Combi-blocks) in dry THF a solution of BuLi (1.6 M solution in hexane, 2.2 eq.) was added dropwise at −78° C. and stirred at −78° C. for 45 min. A solution (1 M) of N-methyl-N-methoxytrifluoroacetamide (1.5 eq.) in dry THF was added at −78° C. to the reaction mixture and stirred for 1 h at −60° C. The reaction mixture was quenched by adding NH4Cl solution, then extracted with DCM. The combined organic layer was washed with brine and dried. Evaporation of the solvent gave a residue (LC-MS (ES+) C6H2F3NO3S requires: 225, found: 226 (M+H)+. Retention time: 2.26 min) that was dissolved in DMF. To the resulting solution (0.5 M), HOBt (1.5 eq.) and EDCI (1.5 eq.) were added and stirring was continued for 1 h. N-benzylmethylamine (1.5 eq.) was added and the reaction mixture was stirred at RT O/N. The crude was purified by RP-HPLC to yield (3%) the title compound as a solid.
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