31374-18-2

Basic information

• Product Name: 7-CHLORO-4-QUINAZOLINOL
• Synonyms: 7-CHLOROQUINAZOLIN-4-OL;7-CHLORO-4(1H)-QUINAZOLINONE;7-CHLORO-4-QUINAZOLINOL;7-CHLORO-4-HYDROXYQUINAZOLINE;7-Chloro-4(3H)-quinazolone;7-Chloroquinazolin-4(3H)-one;7-Chloroquinazolin-4-one;7-chloro-1H-quinazolin-4-one
• CAS NO: 31374-18-2
• Molecular Formula: C₈H₅ClN₂O
• Molecular Weight: 180.5911
• EINECS: 207-219-2
• Product Categories: Alcohols and Derivatives;Heterocycles
• Mol File: 31374-18-2.mol
• Article Data: 72

Chemical Properties

• Melting Point: 251-253 °C
• Boiling Point: 331.7 °C at 760 mmHg
• Flash Point: 154.4 °C
• Appearance: /
• Density: 1.5 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.71
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 0.36±0.20(Predicted)
• CAS DataBase Reference: 7-CHLORO-4-QUINAZOLINOL(CAS DataBase Reference)
• NIST Chemistry Reference: 7-CHLORO-4-QUINAZOLINOL(31374-18-2)
• EPA Substance Registry System: 7-CHLORO-4-QUINAZOLINOL(31374-18-2)

Safety Data

• Hazardous Substances Data: 31374-18-2(Hazardous Substances Data)

Usage

Synthesis Reference(s)

Journal of the American Chemical Society, 68, p. 1305, 1946 DOI: 10.1021/ja01211a058

InChI:InChI=1/C8H5ClN2O/c9-5-1-2-6-7(3-5)10-4-11-8(6)12/h1-4H,(H,10,11,12)

Synthetic route

formamide (77287-34-4, 77287-35-5, 60100-09-6) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With acetic acid; diethylamine at 150℃; for 2h; Product distribution / selectivity;	96.1%
With montmorillonite K-10 for 0.0666667h; microwave irradiation;	94%
at 130 - 160℃; for 5h;	90.7%

formamidine acetic acid (3473-63-0) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
In water Microwave irradiation;	95%
In 2-methoxy-ethanol at 120℃; for 16h;	88.1%
In 2-methoxy-ethanol Reflux;
In 2-methoxy-ethanol for 18h; Reflux;
In 2-methoxy-ethanol at 130℃;

methanol (67-56-1) + 2-amino-4-chlorobenzonitrile (38487-86-4) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With cobalt(II) nitrate hexahydrate; tris(2-diphenylphosphinoethyl)phosphine; water; caesium carbonate at 150℃; for 36h; Inert atmosphere; Sealed tube;	92%

formamidinium acetate (64392-62-7) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
In 2-methoxy-ethanol for 1.5h; Heating;	89%

formamide (77287-34-4, 77287-35-5, 60100-09-6) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
at 130 - 190℃; for 4.5h;	87.7%

6-amino-7-methoxy-4-(3'-methylanilino)quinazoline (153437-17-3) + ethoxyethoxyethanol (111-90-0) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With formamide	85%

methanol (67-56-1) + 2-amino-4-chlorobenzamide (5900-59-4) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With copper(l) iodide; oxygen; caesium carbonate at 20℃; for 16h; Irradiation;	85%
With [Cp*Ir(2,2′-bpyO)(H2O)]; caesium carbonate at 130℃; for 2h; Microwave irradiation; Green chemistry;	70%
With [Cp*Ir(2,2'-bpyO)(H2O)]; caesium carbonate at 130℃; for 2h; Inert atmosphere; Microwave irradiation;	70%
With oxygen; copper(II) acetate monohydrate; caesium carbonate at 110℃; for 6h;	68%

2-amino-4-chloro-benzoic acid methyl ester (5900-58-3) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With acetic acid; diethylamine at 150℃; for 2h; Product distribution / selectivity;	84.1%
With formic acid at 145℃; for 12h;	81%
Niementowski Quinazolone Synthesis;
for 10h; Reflux;

2-amino-4-chlorobenzamide (5900-59-4) + oxalic acid (144-62-7) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
In 1,4-dioxane at 120℃; for 14h; Green chemistry;	83%

formamidine hydrochloride (6313-33-3) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
at 210℃; for 0.25h; Cycloaddition;	81%

2-amino-4-chlorobenzamide (5900-59-4) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With hydrogenchloride In water; trimethyl orthoformate	77%

4-chloro-2-iodobenzamide (942319-20-2) + formamidine (463-52-5) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 80℃; for 6h; Inert atmosphere;	71%

5-chloro-2-nitrobenzoic acid (2516-95-2) + ammonium formate (16712-16-6, 64165-14-6, 65387-22-6, 70179-79-2, 540-69-2) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With zinc for 0.108333h; microwave irradiation;	70%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + C24H24Cl2N2O6 → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + C24H22Cl2N4O2

Conditions	Yield
at 186℃;	A 16.2% B 51.5%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + C23H22Cl2N2O6 → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + C23H20Cl2N4O2

Conditions	Yield
at 180 - 185℃; for 2h;	A 19.9% B 47.5%

2-amino-4-chlorobenzonitrile (38487-86-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 7-chloroquinazoline-2,4-dione (13165-35-0)

Conditions	Yield
With zinc(II) chloride at 200℃; for 5h; sealed tube;	A 35% B 36%

2-amino-4-chlorobenzamide (5900-59-4) + orthoformic acid triethyl ester (122-51-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With diethylene glycol at 120℃;

2-amino-4-chlorobenzamide (5900-59-4) + trimethyl orthoformate (149-73-5) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
With hydrogenchloride

2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / Et3N / dioxane / 2 h / 20 °C 2: 16.2 percent / 186 °C View Scheme
Multi-step reaction with 2 steps 1: 74.4 percent / Et3N / dioxane / 3 h / 20 °C 2: 19.9 percent / 2 h / 180 - 185 °C View Scheme
With formamide for 5h; Heating / reflux;
Multi-step reaction with 2 steps 1: sulfuric acid / 9 h / Cooling with ice; Reflux 2: formic acid / 12 h / 145 °C View Scheme
Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; ammonium chloride; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 15 h / 20 °C 2: copper(l) iodide; caesium carbonate; oxygen / 16 h / 20 °C / Irradiation View Scheme

1,4-dioxane (123-91-1) + 2-amino-4-chlorobenzamide (5900-59-4) + orthoformic acid triethyl ester (122-51-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one

4-chloro-2-nitro-benzoic acid (6280-88-2) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonium formate; 5%-palladium/activated carbon / ethanol / 6 h / Reflux 2: 4 h / Reflux View Scheme

para-chlorobenzoic acid (74-11-3) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: nitric acid / water / 6 h / 60 °C / Cooling with ice 2: ammonium formate; 5%-palladium/activated carbon / ethanol / 6 h / Reflux 3: 4 h / Reflux View Scheme

orthoformic acid triethyl ester (122-51-0) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
at 100℃; for 17h;
With ammonium acetate In ethanol at 110℃; for 0.333333h; Microwave irradiation;

2-Amino-4-chlorobenzoic acid (89-77-0) + formamidine (463-52-5) → 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2)

Conditions	Yield
In 2-methoxy-ethanol at 130℃;

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 4-bromoethylbutanoate (2969-81-5) → 4-(7-chloro-4-oxo-4H-quinazolin-3-yl)-butyric acid ethyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 10h; Alkylation;	97%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + methyl 1-phenylprop-2-enyl carbonate (160879-62-9) → 7-chloro-3-((S)-1-phenylallyl)quinazolin-4(3H)-one

Conditions	Yield
With chloro(1,5-cyclooctadiene)rhodium(I) dimer; (R)-(+)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-di-tert-butylphenyl)phosphine] In 1,2-dichloro-ethane at 80℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;	96%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + benzylamine (100-46-9) → N-benzyl-7-chloroquinazolin-4-amine (477861-82-8)

Conditions	Yield
With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane at 125℃; for 2h;	95%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) → 4,7-dichloroquinazoline (2148-57-4)

Conditions	Yield
With trichlorophosphate at 100℃; for 3h;	94.828%
With oxalyl dichloride In chloroform; N,N-dimethyl-formamide at 20 - 60℃;	80%
With oxalyl dichloride In chloroform; N,N-dimethyl-formamide at 60℃; Cooling with ice;	80%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (1539-59-9) → 7-chloro-2-cyclohexylquinazolin-4(3H)-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one; 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester With trifluoroacetic acid In 2,2,2-trifluoroethanol at 20℃; for 4h; Sealed tube; Irradiation; Inert atmosphere; Stage #2: In 2,2,2-trifluoroethanol at 20℃; for 4h;	93%
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one; 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester With trifluoroacetic acid In 2,2,2-trifluoroethanol at 35℃; for 4h; Irradiation; Inert atmosphere; Sealed tube; Stage #2: In 2,2,2-trifluoroethanol for 4h; Irradiation; Inert atmosphere;	93%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) → 7-chloro-6-nitro-4(3H)-quinazolinone (53449-14-2)

Conditions	Yield
With sulfuric acid; nitric acid at 50 - 90℃;	92.6%
With sulfuric acid; nitric acid at 0 - 90℃; for 3h;	72%
With sulfuric acid; nitric acid at 90℃; for 3h; Cooling with ice;	71.2%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 1-oxa-6-aza-spiro-[2.5]octane-6-caboxylic acid tert-butyl ester (147804-30-6) → tert-butyl 4-[(7-chloro-4-oxo-3,4-dihydroquinazolin-3-yl)methyl]-4-hydroxypiperidine-1-carboxylate (1426340-66-0)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃;	85%
With caesium carbonate In N,N-dimethyl-formamide at 80℃;	85%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;	83.7%
With caesium carbonate In N,N-dimethyl-formamide at 80℃;	68%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 1-bromomethyl-4-nitro-benzene (100-11-8) → 7-chloro-3-(4-nitro-benzyl)-3H-quinazolin-4-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium methylate In methanol for 0.166667h; Metallation; Stage #2: 1-bromomethyl-4-nitro-benzene In methanol at 20℃; for 0.5h; Condensation;	81.6%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 2-bromo-1-phenyl-1-propanone (2114-00-3) → 7-chloro-3-(1-methyl-2-oxo-2-phenyl-ethyl)-3H-quinazolin-4-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium methylate In methanol for 0.166667h; Metallation; Stage #2: 2-bromo-1-phenyl-1-propanone In methanol at 20℃; for 0.5h; Condensation;	79.4%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 2-bromo-4'-fluoroacetophenone (403-29-2) → 7-chloro-3-[2-(4-fluoro-phenyl)-2-oxo-ethyl]-3H-quinazolin-4-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium methylate In methanol for 0.166667h; Metallation; Stage #2: 2-bromo-4'-fluoroacetophenone In methanol at 20℃; for 0.5h; Condensation;	77.8%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 4-bromomethyltrifluoromethylbenzene (402-49-3) → 7-chloro-3-(4-trifluoromethyl-benzyl)-3H-quinazolin-4-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium methylate In methanol for 0.166667h; Metallation; Stage #2: 4-bromomethyltrifluoromethylbenzene In methanol at 20℃; for 0.5h; Condensation;	76.9%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + cyclohexane (110-82-7) → 7-chloro-2-cyclohexylquinazolin-4(3H)-one

Conditions	Yield
With sodium azide; bis-[(trifluoroacetoxy)iodo]benzene In 2,2,2-trifluoroethanol at 20℃; for 3h;	76%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + α-bromoacetophenone (70-11-1) → 7-chloro-3-(2-oxo-2-phenyl-ethyl)-3H-quinazolin-4-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium methylate In methanol for 0.166667h; Metallation; Stage #2: α-bromoacetophenone In methanol at 20℃; for 0.5h; Condensation;	75%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + 4-Fluorobenzyl bromide (459-46-1) → 7-chloro-3-(4-fluorophenylmethyl)quinazolin-4(3H)-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium methylate In methanol for 0.166667h; Metallation; Stage #2: 4-Fluorobenzyl bromide In methanol at 20℃; for 0.5h; Condensation;	74.5%

7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) + chloroacetone (78-95-5) → 7-chloro-3-(2-oxopropyl)quinazolin-4(3H)-one

Conditions	Yield
Stage #1: 7-chloro-3,4-dihydroquinazolin-4-one With sodium hydride In 1-methyl-pyrrolidin-2-one at 20℃; for 0.5h; Stage #2: chloroacetone In 1-methyl-pyrrolidin-2-one at 20℃; for 0.5h;	74%

4-vinylpyridine (100-43-6) + 7-chloro-3,4-dihydroquinazolin-4-one (31374-18-2) → 7-chloro-3-(2-(pyridin-4-yl)ethyl)quinazolin-4(3H)-one

Conditions	Yield
With scandium tris(trifluoromethanesulfonate) In toluene at 110℃; Inert atmosphere;	73%

Upstream product

• 5900-59-4 2-amino-4-chlorobenzamide 
• 122-51-0 orthoformic acid triethyl ester 
• 64392-62-7 formamidinium acetate 
• 89-77-0 2-Amino-4-chlorobenzoic acid 
• 5900-58-3 2-amino-4-chloro-benzoic acid methyl ester 
• 77287-34-4 formamide 
• 67-56-1 methanol 
• 144-62-7 oxalic acid 
• 20353-93-9 [3-(dimethylamino)-2-azaprop-2-en-1-ylidene]-dimethylammonium chloride 
• 161830-29-1 6-nitro-7-chloro-4-(3-methylanilino)quinazoline 
• 111-90-0 ethoxyethoxyethanol 
• 2148-57-4 4,7-dichloroquinazoline 
• 3473-63-0 formamidine acetic acid 
• 179688-72-3 6-amino-7-methoxy-4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazoline 

Downstream Products

• 161830-29-1 6-nitro-7-chloro-4-(3-methylanilino)quinazoline 
• 53449-14-2 7-Chloro-6-nitro-quinazolin-4-one 
• 1360430-59-6 N-(4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)acrylamide 
• 1360430-60-9 N-(4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)-3-(dimethylamino)propanamide 
• 1360430-71-2 3-chloro-N-(4-(3-Chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)propanamide 
• 1360430-61-0 N-(4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)-3-piperidin-1-ylpropanamide 
• 1360430-62-1 N-(4-((3-chloro-4-fluorophenyl)amino)-7-ethoxyquinazolin-6-yl)-3-morpholinopropanamide 
• 936954-09-5 7-ethoxy-6-nitroquinazolin-4(1H)-one 
• 1360430-70-1 N-(3-chloro-4-fluorophenyl)-7-ethoxy-6-nitroquinazoline-4-amine 
• 1269662-90-9 N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine 
• 858465-96-0 7-phenylquinazolin-4(3H)-one 
• 1384181-36-5 N-((6-(2-methylpyridin-4-yl)pyridin-3-yl)methyl)-7-phenylquinazolin-4-amine 
• 1384182-07-3 4-chloro-7-phenylquinazoline 
• 1012054-73-7 N₁-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-N₅-hydroxyglutaramide 

Relevant articles and documents

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Synthesis of alkylamino quinazolines and anti-tumor activity thereof

The present invention provides a compound represented by formula (I), or a pharmaceutically acceptable salt, or ester, or prodrug thereof. The invention further provides a compound represented by the formula (I) or a pharmaceutically acceptable salt or ester, or a synthetic method of the prodrug and an application of the compound in preparation of a medicament for treating tumors.

Design, synthesis, biological evaluation and structure-activity relationship study of quinazolin-4(3H)-one derivatives as novel USP7 inhibitors

Recent research has indicated that the abnormal expression of the deubiquitinase USP7 induces tumorigenesis via multiple cell pathways, and in particular, the p53-MDM2-USP7 pathway is well understood. USP7 is emerging as a promising target for cancer therapy. However, there are limited reports on USP7 inhibitors. Here we report design, synthesis and biological evaluation of novel quinazolin-4(3H)-one derivatives as potent USP7 inhibitors. Our results indicated that the compounds C9 and C19 exhibited the greatest potency against the USP7 catalytic domain, with IC50 values of 4.86 μM and 1.537 μM, respectively. Ub-AMC assays further confirmed IC50 values of 5.048 μM for C9 and 0.595 μM for C19. MTT assays indicated that gastric cancer MGC-803 cells were more sensitive to these compounds than BGC-823 cells. Flow cytometry analysis revealed that C9 restricted cancer cell growth at the G0/G1 and S phases and inhibited the proliferation and clone formation of MGC-803 cells. Further biochemical experiments indicated that C9 decreased the MDM2 protein level and increased the levels of the tumour suppressors p53 and p21 in a dose-dependent manner. Docking studies predicted that solvent exposure of the side chains of C9 and C19 would uniquely form hydrogen bonds with Met407 of USP7. Additionally, C9 exhibited a remarkable anticancer effect in a zebrafish gastric cancer MGC-803 cell model. Our results demonstrated that quinazolin-4(3H)-one derivatives were suitable as leads for the development of novel USP7 inhibitors and especially for anti-gastric cancer drugs.