1,2-Dichloroethane → HCID 44817757、化合物

3-(tert-Butoxycarbonylamino-methyl)-benzoic acid, (754 mg, 3.0 mmol), EDC (958.5 mg, 5.0 mmol), and HOBt (540.5 mg, 5.0 mmol) were combined in a reaction vial and DMF (5 mL) then N-methylmorpholine (0.549 mL, 5.0 mmol) were added. The reaction mixture was agitated for 1 h, then 4-dimethylaminomethyl-phenylamine (451 mg, 3 mmol) was added as a solution in 1 mL DMF. Shaking was continued 48 h. The reaction mixture was diluted to 50 mL with dichloromethane, washed with NaHCO3 (satd. aq., 1×25 mL, and brine (1×25 mL), dried and evaporated to a residue weighing approximately 2 g, which was taken up in 10 mL dichloromethane and treated with Si-isocyanate (silica-bound alkyl isocyanate; 1.2 g, 14.4 mmol). The resulting mixture was agitated overnight and the silica reagent was filtered. The filtrate was evaporated to provide the intermediate ([3-(4-dimethylaminomethyl-phenylcarbamoyl)-benzyl]-carbamic acid tert-butyl ester), which was treated directly with a solution of TFA (2 mL) in dichloromethane (5 mL). The reaction mixture was stirred for 2 h, then the solvents were evaporated and the residue was re-dissolved in dichloromethane (25 mL). This solution was washed with NaHCO3 (satd. aq., 1×25 mL). To this wash was added 1 g Na2CO3 and the wash was extracted with dichloromethane (2×25 mL). The organic extracts were combined and washed with brine (1×25 mL), dried and evaporated to 160 mg of a solid (3-aminomethyl-N-(4-dimethylaminomethyl-phenyl)-benzamide-20%-2 steps) which was used directly. This intermediate (28.3 mg, 0.1 mmol) was dissolved in DMF (1 mL), and 4-isocyanato-1,2-dimethoxy-benzene (23.3 mg, 0.13 mmol) was added. The resulting mixture was agitated for 48 hours, then was purified directly by preparative HPLC using an acetonitrile/water/formic acid gradient. The title compound was collected as a formate salt (31 mg, 67% yield), MS analysis electrospray, 426 (M+H).

1. stirringShaking
2. waitwas continued 48 h
3. washwashed with NaHCO3 (satd
4. dry with materialaq., 1×25 mL, and brine (1×25 mL), dried
5. customevaporated to a residue
6. stirringThe resulting mixture was agitated overnight
7. filtrationthe silica reagent was filtered
8. customThe filtrate was evaporated

ORDレコード

ord-fbdda8b74822497dba30355185327ba2

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08093266B2