23680-84-4

Basic information

• Product Name: 2-Chloro-4-amino-6,7-dimethoxyquinazoline
• Synonyms: QUINAZOLINAMINE;TIMTEC-BB SBB000787;4-Quinazolinamine, 2-chloro-6,7-dimethoxy-;4-AMINO-2-CHLORO-6,7-DIMETHOXYQUINAZOLINE;4-AMINO-2-CHLORO-6,7-DIMETHOXYQUINOZOLINE;4-AMINO-2-CHLORO-6,7-DIMETHOXY-QUINZOLINE;2-CHLORO-4-AMINO-6,7-DIMETHOXYQUINAZOLINE;2-CHLORO-6,7-DIMETHOXY-4-AMINOQUINAZOLINE
• CAS NO: 23680-84-4
• Molecular Formula: C₁₀H₁₀ClN₃O₂
• Molecular Weight: 239.66
• EINECS: 245-821-7
• Product Categories: Quinolines, Quinazolines and derivatives;BUILDING BLOCKS;Doxazosin;intermediate of terazosin);(intermediate of doxazosin);Heterocyclic Compounds;Bases & Related Reagents;Heterocycles;Nucleotides;Alfuzosin Hydrochloride;Doxazosin Mesylate;Amines;Intermediates
• Mol File: 23680-84-4.mol

Chemical Properties

• Melting Point: 262-268 °C (dec.)(lit.)
• Boiling Point: 374 °C at 760 mmHg
• Flash Point: 180 °C
• Appearance: off-white solid
• Density: 1.5062 (rough estimate)
• Vapor Pressure: 8.63E-06mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Sparingly, Heated), Methanol (Slightly, Heated)
• PKA: 4.35±0.30(Predicted)
• Water Solubility: 1.418g/L at 25℃
• BRN: 747463
• CAS DataBase Reference: 2-Chloro-4-amino-6,7-dimethoxyquinazoline(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-4-amino-6,7-dimethoxyquinazoline(23680-84-4)
• EPA Substance Registry System: 2-Chloro-4-amino-6,7-dimethoxyquinazoline(23680-84-4)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• F: 10
• HazardClass: IRRITANT
• Hazardous Substances Data: 23680-84-4(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Intermediate in the production on Terazosin.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 20, p. 146, 1977 DOI: 10.1021/jm00211a031

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C10H10ClN3O2/c1-15-7-3-5-6(4-8(7)16-2)13-10(11)14-9(5)12/h3-4H,1-2H3,(H2,12,13,14)

Upstream product

• 27631-29-4 2-chloro-6,7-dimethoxy-3H-quinazolin-4-one 
• 81745-83-7 pyridin-2-ylzinc(ll) bromide 
• 192869-38-8 4-Amino-2-chloro-6,7-dimethoxy-5-iodoquinazoline 
• 2150-38-1 methyl 3,4-dimethoxybenzoate 
• 26791-93-5 methyl 4,5-dimethoxy-2-nitrobenzoate 
• 26759-46-6 methyl 2-amino-4,5-dimethoxybenzoate 
• 28888-44-0 2,4-dihydroxy-6,7-dimethoxyquinazoline 
• 28888-44-0 6,7-dimethoxy-1H-quinazoline-2,4-dione 
• 607-68-1 2,4-dichloroquinazoline 
• 157459-53-5 3,4-dimethoxy-6-cyanoaniline-1-yl formamide 
• 4998-07-6 4,5-dimethoxy-2-nitro-benzoic acid 
• 4959-60-8 4,5-dimethoxy-2-nitrobenzamide 
• 5004-88-6 4,5-dimethoxyanthranilamide 
• 6315-89-5 3,4-dimethoxyaniline 

Downstream Products

• 84050-21-5 4-amino-6,7-dimethoxy-2-(4-formylpiperazino)quinazoline hydrochloride 
• 108297-16-1 1-(4-amino-6,7-dimethoxy-quinazolin-2-yl)-piperidine-4-carboxylic acid benzyl-methyl-amide 
• 84050-18-0 4-amino-2-(4-cinnamoylpiperazino)-6,7-dimethoxyquinazoline hydrochloride 
• 84050-35-1 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(4-bromo-phenyl)-propenone; hydrochloride 
• 84050-30-6 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(2-methoxy-phenyl)-propenone; hydrochloride 
• 84050-31-7 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(3-methoxy-phenyl)-propenone; hydrochloride 
• 84050-32-8 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(2-ethoxy-phenyl)-propenone; hydrochloride 
• 84050-33-9 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(4-isopropoxy-phenyl)-propenone; hydrochloride 
• 134749-42-1 6,7-dimethoxy-2-(1-phenyl-3-thiosemicarbazido)-4-aminoquinazoline 
• 65189-53-9 N-[3-(4-Amino-6,7-dimethoxy-quinazolin-2-ylamino)-propyl]-benzamide; hydrochloride 
• 96649-42-2 N²-[2-(2,6-Dimethoxy-phenoxy)-ethyl]-6,7-dimethoxy-N²-methyl-quinazoline-2,4-diamine 
• 70978-84-6 6,7-Dimethoxy-2-[4-(2-phenoxy-ethoxy)-piperidin-1-yl]-quinazolin-4-ylamine; hydrochloride 
• 65189-24-4 N¹,N²-dimethyl-N²-(phenylmethyl)-N¹-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1,3-propanediamine 
• 65189-44-8 N-{2-[(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-methyl-amino]-ethyl}-N-methyl-benzamide 

Relevant articles and documents

Zinc-mediated intramolecular acyl and imino transfer reactions of aryl iodides

A method for the coupling of acyl and imino substituents to the sterically encumbered 5-position of a 4-aminoquinazoline was developed. Starting with a 4-amino-5-iodoquinazoline, the method employs a facile intramolecular zinc-mediated transfer from the 4-amino group to the iodo-bearing carbon. The method was found to be effective for a variety of substituents, in particular a pyridyl group required for the synthesis of Pfizer's prostate selective α1 antagonist candidate for the treatment of benign prostatic hyperplasia, UK-338,003.

Quest for a potent antimalarial drug lead: Synthesis and evaluation of 6,7-dimethoxyquinazoline-2,4-diamines

Quinazolines have long been known to exert varied pharmacologic activities that make them suitable for use in treating hypertension, viral infections, tumors, and malaria. Since 2014, we have synthesized approximately 150 different 6,7-dimethoxyquinazoline-2,4-diamines and evaluated their antimalarial activity via structure-activity relationship studies. Here, we summarize the results and report the discovery of 6,7-dimethoxy-N4-(1-phenylethyl)-2-(pyrrolidin-1-yl)quinazolin-4-amine (20, SSJ-717), which exhibits high antimalarial activity as a promising antimalarial drug lead.

Synthetic method for 2-chloro-4-amino-6,7-dimethoxy quinazoline

The invention discloses a synthetic method for 2-chloro-4-amino-6,7-dimethoxy quinazoline. The synthetic method comprises the following steps: 1) preparing 3,4-dimethoxyphenyl isocyanate; 2) preparing 3,4-dimethoxyphenyl cyanourea; 3) preparing a 2-chloro-4-amino-6,7-dimethoxy quinazoline crude product; and 4) preparing a 2-chloro-4-amino-6,7-dimethoxy quinazoline fine product. The synthetic method disclosed by the invention simplifies reaction steps and increases the product yield; reaction conditions are optimized, so that reactants react more sufficiently, and therefore, generation of byproducts is reduced, production efficiency is improved, reactants are prevented from being oxidized, reaction is more complete, the target object can be obtained by direct filtering and drying during post-treatment, and the yield is stable.

Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism

Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α1-blockers and AII-antagonists it was planned to develop dual α1- and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual α1- and AII-antagonists on rat aortic strips for the blockade of known α1- and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was found to be the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was found to be equipotent to losartan. These findings shed a new light on the structural requirements for both α1- as well as AII-receptor antagonists.

Molecular features of the prazosin molecule required for activation of Transport-P

Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.

A NOVEL PROCESS FOR THE PREPARATION OF 2-HALO-4-AMINOQUINAZOLINES

2-Halo-4-aminoquinazolines are produced by a one-step process involving intramolecular cyclization of appropriately substituted formamide derivatives in the presence of phosphorous oxyhalides. Exemplary of the process is the intramolecular cyclization of 3,4-dimethoxy-6-cyanoaniline-1-yl formamide in the presence of phosphorous oxychloride to 2-chloro-4-amino-6,7-dimethoxyquinazoline. These chemical compounds are utilized as intermediates in the preparation of some of the important antihypertensive agents e.g. 2-chloro-4-amino-6,7-dimethoxyquinazolines is used for the synthesis of alfuzosin hydrochloride.

A modified synthesis of iodoazidoaryl prazosin.

The antihypertension agent iodoazidoaryl prazosin (IAAP) has been made using a convergent route involving addition of an acylated piperazine 7 to 2-chloroquinazoline 5. IAAP has been shown to function as a multidrug resistance (MDR) reversal agent and bind to P-glycoprotein, a transmembrane transport protein. A study is also reported involving palladium-catalyzed substitution with amine heterocycles. With N,N-bis(2,6-diisopropyl)dihydroimidazolium chloride (10) as the ligand (2 mol %) for palladium(II) acetate (2 mol %) in THF at room temperature, morpholine added to 5 in 81% yield.

Process for preparing quinazolines

2-Halo-4-aminoquinazolines are produced by a two-step process involving cyclization of 1-phenyl-3-cyanoureas or 1-phenyl-3-cyanothioureas in the presence of phosphorus halides and phosphorus oxyhalides to provide a phosphoquinazoline intermediate which is hydrolyzed to the quinazoline. Exemplary of the process is the intramolecular cyclization of 1-(3,4-dimethoxyphenyl)-3-cyanourea in the presence of phosphorus pentachloride and phosphorus oxychloride to a phosphoquinazoline intermediate which is subsequently hydrolyzed with formic acid to 2-chloro-4-amino-6,7-dimethoxy-quinazoline. The 2-halo-4-aminoquinazolines of the instant process are particularly valuable as intermediates in the preparation of 4-amino-2-(4-substituted-piperazin-l-yl)quinazolines useful in the treatment of cardiovascular disease, e.g. hypertension.

Synthesis and identification of the major metabolites of prazosin formed in dog and rat

The 6 O demethyl and 7 O demethyl analogues of the new antihypertensive drug prazosin [2 [4 (2 furoyl) piperazin 1 yl] 4 amino 6,7 dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate ten step reaction sequences starting from isovanillin and vanillin, respectively. The 6 O demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7 O demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2 (1 piperazinyl) 4 amino 6,7 dimethoxyquinazoline and 2,4 diamino 6,7 dimethoxyquinazoline, are also described. All four metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.