1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-(3-Methylphenyl)urea

To a solution of N-[(3RS)-1-hydroxycarbonylmethyl-5-(2-fluorophenyl)-2,3-dihydro-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea (0.295 g) and 8-methyl-3,8-diazabicyclo[3.2.1]octane dihydrochloride (0.189 g) in N,N-dimethylformamide (10 ml) was added l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (0.150 g), 1-hydroxy-1H-benzotriazole monohydrate (0.120 g) and a solution of triethylamine (0.255 g) in N,N-dimethylformamide (2 ml). The. mixture was stirred overnight at ambient temperature. Then the mixture was heated at 80° C. for 1 hour. The mixture was concentrated in vacuo. The residue was treated with water, alkalized with sodium carbonate and extracted with chloroform. The extract was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and methanol (50:1) to give N-[(3RS)-5-(2-fluorophenyl)-I-(8-methyl-3,8-diazabicyclo[3.2.1]-oct-3-yl)]carbonylmethyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea (0.300 g) as a colorless crystal.

1. temperatureThen the mixture was heated at 80° C. for 1 hour
2. concentrationThe mixture was concentrated in vacuo
3. additionThe residue was treated with water
4. extractionextracted with chloroform
5. dry with materialThe extract was dried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and methanol (50:1)

ORDレコード

ord-09b67994194446b9ad034c45b81506b5

出典データセット

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05763437