文档介绍：药物详细合成路线
Chemical Name：
3-(Cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
Generic Name：
罗***司特;Roflumilast
Other Names：
Roflumilast;APTA-2217;BY-217;Daxas
CAS：
162401-32-3
Formula：
C17H14Cl2F2N2O3
Mole Weight：
structure：
Company：
Altana (Originator), Tanabe Seiyaku (Licensee), Pfizer (Codevelopment)
Usage：
Antiallergy/Antiasthmatic Drugs, Asthma Therapy, Chronic Obstructive Bronchitis, Agents for, Chronic Obstructive Pulmonary Diseases (COPD), Treatment of, RESPIRATORY DRUGS, Phosphodiesterase IV Inhibitors
Route 1
Condensation of the benzaldehyde derivative (I) with chlorodifluoromethane (II) by means of NaOH and benzyltrimethylammonium chloride (BTMA) in dioxane/water gives 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde (III), which is oxidized with NaClO2 and sulfamic acid in acetic acid to yield the corresponding benzoic acid derivative (IV). The reaction of (IV) with SOCl2 in refluxing toluene affords the acyl chloride (V), which is finally condensed with 3,5-dichloropyridin-4-amine (VI) by means of NaH in THF.
Intermediates:
Serial No.
2-(allyloxy)-2-(2,4-dichlorophenyl)acetic acid
(II)
5,6-dimethoxy-2-benzofuran-1,3-dione
(VI)
tert-butyl 4-hydroxy-1-naphthylcarbamate
(I)
tert-butyl 4-[2-(4-morpholinyl)ethoxy]-1-naphthylcarbamate
(III)
tert-butyl (2R)-2-amin