Afloqualone

6-amino-2-(fluoromethyl)-3-(2-methylphenyl)quinazolin-4-one

HQ 495, C033541, QA-3735, UNII:CO4U2C8ORZ

Afloqualone; 56287-74-2; Arofuto; Aroft; Afloqualon; Afloqualone [INN:JAN]

Afloqualone (Arofuto) is a quinazolinone family GABAergic drug and is an analogue of methaqualone developed in the 1970s by a team at Tanabe Seiyaku.^[1] It has sedative and muscle-relaxant effects resulting from its agonist activity at the β subtype of the GABA_areceptor ,^[2] and has had some clinical use, although it causes photosensitization as a side-effect that can cause skin problems such as dermatitis.^[3]

PATENT

CN 106496145

PATENT

CN 106496144

https://patents.google.com/patent/CN106496144A/en

Example 1:

[0027] A-fluoro-quinolin-one process, comprising the steps of:

[0028] A. To the hydrogenation apparatus 10g 6- nitro-2- (fluoromethyl) -3- (2-methylphenyl) -4- (3H) -1,3- phthalazinone , 150ml acid content of 0.1 ~ 0.4N n-butanol solution of acetic acid, lg palladium ruthenium bimetallic catalyst, hydrogen pressure 0.02 ~ 0.4MPa, reaction temperature of 25-50 ° C, after 1 hour, filtered to give the filtrate ;

[0029] B. washed catalyst with ethanol, at normal temperature, under reduced pressure to obtain a solution ⑴;

[0030] C. was added to the filtrate and the solution ⑴ water, 0.1N sodium hydroxide solution was added, the pH adjusted to 10.2 to 11.0, and stirred at 50-60 ° C 0.5 h, cooled to room temperature and filtered to give the crude fluoro-quinolin-one;

[0031] D.-fluoro-quinolin per gram of the recrystallization solvent was added 5 ~ 15ml crude ketone, wherein the recrystallization solvent is a volume ratio of 1: 1: 0.2 in a solution of isopropanol (m), a solution of acid butyl ester (II ) and water mixture; crystallized at room temperature, filtered to give a fluorine methaqualone.

[0032] Example 2:

[0033] A-fluoro-quinolin-one process, comprising the steps of:

[0034] A. hydrogenation apparatus added to 20g 6- nitro _2_ (fluoromethyl) -3- (2_-methylphenyl) -4- (3-1,3-phthalazinone buckle, acid content of the acid-containing 240ml 0.1 ~ 0.4N ethanol solution of hydrochloric acid, lg palladium ruthenium bimetallic catalyst, hydrogen pressure 0.02 ~ 0.4MPa, reaction temperature of 25-50 ° C. after 0.5 hours the reaction was filtered to obtain filtrate;

[0035] B. washed catalyst with ethanol, at normal temperature, under reduced pressure to obtain a solution ⑴;

[0036] C. was added to the filtrate and the solution ⑴ water, 0.1N sodium hydroxide solution was added, the pH adjusted to 10.2 to 11.0, and stirred at 50-60 ° C 1 hour, cooled to room temperature and filtered to give the crude fluoro-quinolin-one;

[0037] D.-fluoro-quinolin added per gram of crude ketone was recrystallized from 5 ~ 15ml of the solvent, wherein the recrystallization solvent is a volume ratio of 1: o.2: methanol solution of i (m), an ethyl acetate solution (II ) and water mixture; crystallized at room temperature, filtered to give a fluorine methaqualone.

[0038] Example 3:

[0039] – quinolin-fluoro-one kind of process, comprising the steps of:

[0040] A. Add 5g 6- nitro apparatus _2_ hydride (fluoromethyl) -3- (2-methylphenyl) -4- (3-1,3-Perot phthalazinone, 80ml methanol containing an acid in an amount of 0.1 ~ 0.4N solution of sulfuric acid, lg palladium ruthenium bimetallic catalyst, hydrogen pressure 0.02 ~ 0.4MPa, reaction temperature of 25-50 ° C. after 1.5 hours the reaction was filtered to obtain filtrate;

[0041] B. the catalyst was washed with ethanol, normal temperature under reduced pressure to obtain a solution (the I);

[0042] C. was added to the filtrate and the solution (I) water, 0.1N sodium hydroxide solution was added, the pH adjusted to 10.2 to 11.0, and stirred at 50-60 ° C 1 hour, cooled to room temperature and filtered to give fluoro-quinolin-one Crude;

[0043] D. methaqualone fluorine per gram of crude product were added 5 ~ 15ml recrystallization solvent, wherein the recrystallization solvent is a volume ratio of 1: 0.2: 0.2 ethanol solution (m), carboxylic acid butyl ester (II) and water mixture; crystallization at room temperature, and filtered to give fluoro-quinolin-one.

PAPER

6-Amino-2-(fluoromethyl)-3-(2-methylphenyl)quinazolin-4(3H)-one
Acta Crystallographica, Section E: Structure Reports Online (2007), 63, (7), o3109

http://scripts.iucr.org/cgi-bin/paper?S1600536807026670

PAPER

Synthesis of the metabolites of afloqualone and related compounds
Chemical & pharmaceutical bulletin (1983), 31, (4), 1158-65.

Seven main metabolites (3-9) of afloqualone (1, 6-amino-2-fluoromethyl-3-(o-tolyl)-4 (3H)-quinazolinone and related 4 (3H)-quinazolinone derivatives were synthesized. The metabolites 4 and 5 containing a sulfur atom were prepared by the reaction of 6-acetamido-2-chloromethyl-3-(o-tolyl)-4 (3H)-quinazolinone (11) with NaSCH₃ followed by oxidation with H₂O₂. Reaction of 11 and N-acetyl-L-cysteine gave the mercapturic acid-conjugated metabolite 6. Condensation of 2-fluoroacetamido-5-nitrobenzoic acid (19) and 2-amino-benzyl alcohol (20) with dicyclohexylcarbodiimide (DCC) in the presence of 1-hydroxy-benzotriazole afforded 2-fluoromethyl-3-(o-hydroxymethylphenyl)-6-nitro-4 (3H)-quinazolinone (21), which was converted to the metabolites 7 and 8. Treatment of the 2-bromomethyl-4 (3H)-quinazolinone (24) with AgBF₄-H₂O in dimethylsulfoxide (DMSO) gave the 2-hydroxymethyl metabolite 9. None of the main metabolites (2-9) showed significant central nervous system depressant activity

https://www.jstage.jst.go.jp/article/cpb1958/31/4/31_4_1158/_article

References

Afloqualone

Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	none
Legal status
Legal status	US: Unscheduled
Identifiers
IUPAC name[show]
CAS Number	56287-74-2
PubChem CID	2040
ChemSpider	1960
UNII	CO4U2C8ORZ
KEGG	D01638
ChEMBL	CHEMBL2105918
Chemical and physical data
Formula	C16H14FN3O
Molar mass	283.3
3D model (JSmol)	Interactive image

//////////////Afloqualone, HQ 495, アフロクアロン , C033541, QA-3735, UNII:CO4U2C8ORZ, 4831

CC1=CC=CC=C1N2C(=NC3=C(C2=O)C=C(C=C3)N)CF

Afloqualone