1,1,3,3-Tetramethylguanidine → HCID 86586335, compound

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Reaction Conditions

Reaction Steps

1,1,3,3-Tetramethylguanidine (53 μL, 0.42 mmol) is added to a solution of rac.-N-[2,6-dimethyl-4-[5-[(1H-indol-4-yl)methylamino]tetrazol-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 330; 108.3 mg, 0.2 mmol) in tetrahydrofuran (2 mL) at −40° C. The solution is stirred at −40° C. for 5 min and then 2,4-di-methylthiazole-4-carboxaldehyde (Example 43; 56.4 mg, 0.4 mmol) is added. The solution is stirred at −40° C. for 1 h and then allowed to stir at room temperature for 4 h. The solution is quenched with pH 6 phosphate buffer, diluted with ethyl acetate (15 mL) and the separated organic layer is washed with pH 6 phosphate buffer (10 mL) and brine (10 mL). The organic phase is dried (MgSO4), filtered, evaporated under reduced pressure. The residue is chromatographed over silica gel (increasing percentages of ethyl acetate in petroleum ether) and the appropriate fractions are combined and evaporated to yield to give (Z)-2-[2,6-dimethyl-4-[5-[(1H-indol-4-yl)methylamino]tetrazol-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester.

Provenance & Evidence