Growth Hormone Releaser Benzimidazolidinones

Okazaki et al, US Patent 6,939,887 (September 6, 2005) Assignee Sumitomo Pharmaceuticals Co., Ltd Utility Treatment of Growth Hormone Deficiency 

Invention Significance Growth hormone deficiency results in symptoms 

2-Chloroaniline (1.4463 g) dissolved in 10ml pyridine was treated withl.3ml ethyl chloroformate under ice-cooling, then stirred 1 hour. The solution was then treated with 1M HC1 and extracted with EtOAc. The organic layer was washed with 1M HC1, brine, dried with MgS04, concentrated, and the product isolated in 98% yield. 

Preparation of ethyl 2-chlorophenyl[2,4-dinitro-6-(trifluoromethyl) phenyl] carbamate 

The Step 1 product (62.6 mg) dissolved in 1 ml diglyme was treated with sodium hydride (12.6 mg) and 2-chloro-3,5-dinitrobenzotrifluoride (77.1 mg), then stirred 1 hour at ambient temperature, and treated with 1 M HC1. The mixture was extracted with EtOAc, then washed with 1M HC1 and saturated NaHC03 solutions, dried, and concentrated. The residue was purified by preparative TLC using hexane/EtOAc, 3 1, and the product isolated in 93% yield. 

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