1,1'-Carbonyldiimidazole → HCID 68847086, compound

Temperature

70 °C

To 1.0 g of carboxylic acid 1 in a 100 mL round bottom flask equipped with a septa under nitrogen, was added 20 mL of dry dichloroethane (DCE). To this solution was then added 1.2 equivalents of Diphenylphosphorylazide (DPPA) in one portion followed by 3 equivalents of triethylamine. The solution was stirred overnight at room temperature. The reaction progress was followed by an analytical Shimadzu LC/MS. The crude mixture was passed through a 24 g SiliCycle/Isco silica gel cartridge with DCE to give acyl azide 2 as a light yellow foam after solvent evacuation (50-65% yield). The acyl azide was found to be stable at room temperature in a vacuum desiccator for up to one month. To 0.3 mmol of acyl azide 2 in 2 mL of dry toluene was added 1.2 equivalents of amine in a Biotage/Personal Chemistry microwave vial. The vial was capped and heated to 100° C. in a Biotage/Personal Chemistry Emrys Optomizer microwave for 25 minutes. The crude reaction mixture was then evacuated to near dryness, taken up in a 1:1 ethyl acetate/hexane mixture and purified by flash chromatography to yield urea 3 (50-55% yield). To 0.15 mmol of intermediate 3 was added 10 equivalents of potassium trimethylsilanolate (TMSOK) and 3 mL of dry tetrahydrofuran. The mixture was stirred at room temperature overnight. After the overnight treatment, the crude product was evacuated to near dryness, taken up in ethyl acetate, and neutralized with 0.5 M HCl. After extraction the solvent was removed to give a near quantitative yield of carboxylic acid 4 (purity >90%) which was used without further purification. To 0.14 mmol of carboxylic acid 4 in 1 mL of dry tetrahydrofuran was added 3 equivalents of carbonyldiimidazole. The solution was heated for 2-3 hours at 70° C. in a one dram vial equipped with a screw cap. At this point, 1.4 equivalents of neat 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was dripped into the mixture followed by the addition of N,N-Dimethylsulfamide (as a solid). The vial was returned to the heating bath and shaken overnight. The crude reaction mixture was then evacuated to dryness and purified using a Shimadzu preparative HPLC to give dimethylamino sulfamide 5 as a yellow amorphous solid (35-50% yield).

1. customwas used without further purification
2. customvial equipped with a screw
3. customcap
4. customThe crude reaction mixture
5. customwas then evacuated to dryness
6. custompurified

ORD record

ord-8d847c0556324737a42f532186a45e4e

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07473688B2