112733-06-9 Usage
Originator
FK 366 ,Fujisawa Pharmaceutical
Uses
Treatment of diabetic neuropathy (aldose reductase inhibitor).
Manufacturing Process
To a solution of 4-bromo-2-fluorobenzylamine and triethylamine in chloroform
was added dropwise a solution of 4-chloro-2-nitrobenzoyl chloride in
chloroform at 0°C with stirring and the mixture was stirred at the same
temperature for 1 h. The reaction mixture was washed in turn with diluted
aqueous hydrochloric acid and water, and then dried. Evaporation of the
solvent followed by recrystallization from diethyl ether gave N-(4-bromo-2-
fluorobenzyl)-4-chloro-2-nitrobenzamide.
A mixture of N-(4-bromo-2-fluorobenzyl)-4-chloro-2-nitrobenzamide and iron
(1.45 g) in acetic acid (66 ml) was stirred at 100°C for 30 min. After cooling,
iron was filtered off. The filtrate was evaporated to give a residue, which was
made alkaline with aqueous 1 N sodium hydroxide and extracted with ethyl
acetate. The extract was washed with water and dried. Removal of the solvent
gave 2-amino-N-(4-bromo-2-fluorobenzyl)-4-chlorobenzamide.
2-Amino-N-(4-bromo-2-fluorobenzyl)-4-chlorobenzamide and N,N'-
carbonyldiimidazole were dissolved in dioxane (50 ml). The solution was
evaporated to give a residue, which was stirred at 150°C for 30 min. After
cooling, the precipitates were collected by filtration and washed with ethanol
to give 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4-
dioxoquinazoline; melting point >280°C.
To a suspension of 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-
2,4-dioxoquinazoline in N,N-dimethylformamide was added sodium hydride
(60% in mineral oil) with stirring at 0°C and the mixture was stirred for 15
min at the same temperature. To this mixture was added ethyl bromoacetate
and the mixture was stirred for 1 h at room temperature. The reaction
mixture was poured into diluted hydrochloric acid and extracted with ethyl
acetate. The extract was washed with brine, dried and evaporated to give a
residue. Thus obtained product was purified by recrystallization from isopropyl
ether to give 2-[3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4-
dioxoquinazolin-1-yl]acetic acid melting point 223°-224°C.
Therapeutic Function
Aldose reductase inhibitor
Check Digit Verification of cas no
The CAS Registry Mumber 112733-06-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,2,7,3 and 3 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 112733-06:
(8*1)+(7*1)+(6*2)+(5*7)+(4*3)+(3*3)+(2*0)+(1*6)=89
89 % 10 = 9
So 112733-06-9 is a valid CAS Registry Number.
InChI:InChI=1/C17H11BrClFN2O4/c18-10-2-1-9(13(20)5-10)7-22-16(25)12-4-3-11(19)6-14(12)21(17(22)26)8-15(23)24/h1-6H,7-8H2,(H,23,24)
112733-06-9Relevant articles and documents
The process development of a novel aldose reductase inhibitor, FK366. Part 1. Improvement of discovery process and new syntheses of 1-substituted quinazolinediones
Goto, Shunsuke,Tsuboi, Hiroyuki,Kanoda, Masami,Mukai, Koji,Kagara, Kooji
, p. 700 - 706 (2003)
This contribution describes part 1 of process development of a novel aldose reductase inhibitor FK366 (1). The original process applied on a laboratory scale was improved from the safety viewpoint to manufacture materials on 500-L scale suitable for toxic
PROCESS FOR PRODUCING QUINAZOLINE DERIVATIVE OR SALT THEREOF
-
, (2008/06/13)
This invention provides a novel industrial process for preparation of a quinazoline derivative (I) represented by the general formula: in which R1 is hydrogen or halogen,R2 is protected carboxy,R3 is ar(lower)alkyl which m
Quinazoline derivatives, compositions thereof and their use in treating diabetic complications
-
, (2008/06/13)
The invention relates to compounds of the formula: STR1 in which R1 and R2 are each hydrogen, halogen, lower alkoxy or halo(lower)alkyl, R3 is dihalophenyl, naphthyl(lower)alkyl, phenyl(lower)alkyl substituted by one or two substituent(s) selected from the group consisting of halogen, lower alkoxy, halo(lower)alkyl and lower alkyl, or thienyl(lower)alkyl, R4 is carboxy or protected carboxy, Y is carbonyl, thiocarbonyl or sulfonyl and Z is lower alkylene, and pharmaceutically acceptable salts thereof, useful in the treatment of diabetic complications.