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

Temperature

-40 °C

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.

1. stirringThe solution is stirred at −40° C. for 1 h
2. stirringto stir at room temperature for 4 h
3. customThe solution is quenched with pH 6 phosphate buffer
4. additiondiluted with ethyl acetate (15 mL)
5. washthe separated organic layer is washed with pH 6 phosphate buffer (10 mL) and brine (10 mL)
6. dry with materialThe organic phase is dried (MgSO4)
7. filtrationfiltered
8. customevaporated under reduced pressure
9. customThe residue is chromatographed over silica gel (increasing percentages of ethyl acetate in petroleum ether)
10. customevaporated
11. customto yield

ORD record

ord-f9a18e3d66ed4ee1bdebb26ad6d556a3

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515124B2