7752-82-1

Basic information

• Product Name: 2-Amino-5-bromopyrimidine
• Synonyms: 2-AMINO-5-BROMOPYRIMIDINE;5-BROMO-2-PYRIMIDINAMINE;5-BROMO-2-PYRIMIDINYLAMINE;5-BROMO-2-AMINOPYRIMIDINE;5-BROMOPYRIMIDIN-2-YLAMINE;TIMTEC-BB SBB000184;5-BROMOPYRIMIDIN-2-AMINE;2-Amino-5-Bormopyrimidine
• CAS NO: 7752-82-1
• Molecular Formula: C₄H₄BrN₃
• Molecular Weight: 174
• EINECS: 2017-001-1
• Product Categories: FINE Chemical & INTERMEDIATES;Amines and Anilines;Heterocycles;Pyridines, Pyrimidines, Purines and Pteredines;Organohalides;Pyrimidine;Aromatics Compounds;Aromatics;Bases & Related Reagents;Nucleotides;Halides;Pyrazines, Pyrimidines & Pyridazines;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Pyrimidines;PyrimidinesHeterocyclic Building Blocks;Heterocycle-Pyrimidine series
• Mol File: 7752-82-1.mol

Chemical Properties

• Melting Point: 241-243 °C(lit.)
• Boiling Point: 340.743 °C at 760 mmHg
• Flash Point: 159.876 °C
• Appearance: White to light beige/Crystalline Powder, Crystals or Flakes
• Density: 1.844 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.649
• Storage Temp.: Refrigerator (+4°C)
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 1.93±0.10(Predicted)
• Water Solubility: Insoluble
• CAS DataBase Reference: 2-Amino-5-bromopyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-5-bromopyrimidine(7752-82-1)
• EPA Substance Registry System: 2-Amino-5-bromopyrimidine(7752-82-1)

Safety Data

• Hazard Codes: Xn,N,Xi
• Statements: 22-36-50/53
• Safety Statements: 26-60-61
• RIDADR: UN 3077 9/PG 3
• WGK Germany: 3
• HazardClass: IRRITANT, IRRITANT-HARMFUL
• PackingGroup: III
• Hazardous Substances Data: 7752-82-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
2-Amino-5-bromopyrimidine is used as a key intermediate in the synthesis of pyridine, pyrimidine, and pyridinone C-nucleoside phosphoramidites. These phosphoramidites are essential building blocks for the development of nucleic acid analogs, which have potential applications in the treatment of viral infections and genetic disorders.
Used in Organic Chemistry:
2-Amino-5-bromopyrimidine is also used as an intermediate in the synthesis of 2-phthalimido-5-bromopyrimidine, which is a valuable precursor for the preparation of various organic compounds and pharmaceuticals.
Used in Antiviral Agent Development:
2-Amino-5-bromopyrimidine serves as an intermediate for the preparation of sulfanilamides and amino acids containing the pyrimidine ring system. The resulting products have potential antiviral properties, making them valuable for the development of new antiviral agents to combat viral diseases.

Synthesis

The synthesis of 2-Amino-5-bromopyrimidine is as follows:The 2-aminopyrimidine (2.5g, 26.29mmol) was dissolved in acetonitrile (25mL) was added N- bromosuccinimide (4.6g, 27.9mmol) under ice-cooling, stirred in the dark overnight at room temperature. Recovery of the solvent under reduced pressure, washed with water (100 mL) was washed, filtered off with suction, and dried in vacuo to give a white solid. Yield: 97%.

storage

Store in cool, well ventilated area. Keep container tightly closed. Light sensitive. Store under argon.

InChI:InChI=1/C4H4BrN3/c5-3-1-7-4(6)8-2-3/h1-2H,(H2,6,7,8)

Synthetic route

2-aminopyrimidine (109-12-6) → 5-bromo-2-aminopyrimidine (7752-82-1)

Conditions	Yield
With N-Bromosuccinimide; ammonium acetate In acetonitrile at 20℃; for 0.0833333h;	100%
With N-Bromosuccinimide; ammonium acetate In acetonitrile at 20℃; for 0.5h;	98%
With N-Bromosuccinimide In acetonitrile at 20℃; Cooling with ice; Darkness;	97%

2-aminopyridine (504-29-0) → 5-bromo-2-aminopyrimidine (7752-82-1)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 20℃; Darkness; Cooling with ice;	97%

2‐aminopyrimidine‐1‐oxide (35034-15-2) → 5-bromo-2-aminopyrimidine (7752-82-1) + 5-bromo-2-aminopyrimidine 1-oxide (84539-23-1)

Conditions	Yield
With hydrogen bromide; sodium nitrite	A 26.7% B 30%

ammonia (7664-41-7) + 5-Bromo-2-chloropyrimidine (32779-36-5) → 5-bromo-2-aminopyrimidine (7752-82-1)

Conditions	Yield
In ethanol at 80℃; Sealed tube;

5-bromo-2-aminopyrimidine (7752-82-1) + 1,2-bis-(chlorodimethylsilyl)ethane (13528-93-3) → 5-bromo-2-(2,2,5,5-tetramethyl-1,2,5-azadisilolidin-1-yl)pyrimidine

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; toluene at -10 - 0℃; for 1h; Inert atmosphere;	100%

5-bromo-2-aminopyrimidine (7752-82-1) + N,N-dimethylacetamide dimethyl acetal (18871-66-4) → N'-(5-bromopyrimidin-2-yl)-N,N-dimethylacetamidine

Conditions	Yield
In ethanol at 120℃; for 18h; Sealed tube;	98%

5-bromo-2-aminopyrimidine (7752-82-1) + phenylboronic acid (98-80-6) → 5-phenyl-pyrimidin-2-ylamine (31408-23-8)

Conditions	Yield
With potassium phosphate tribasic heptahydrate; palladium diacetate In ethylene glycol at 80℃; for 2h; Suzuki coupling;	95%
With potassium phosphate; palladium diacetate In ethylene glycol at 80℃; for 12h;	50.5%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 90℃; for 16h; Inert atmosphere;	28.5%
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane; water for 8h; Heating / reflux;

5-bromo-2-aminopyrimidine (7752-82-1) + 4-fluoroboronic acid (1765-93-1) → 2-amino-5-(4-fluorophenyl)pyrimidine (31408-40-9)

Conditions	Yield
With potassium phosphate tribasic heptahydrate; palladium diacetate In ethylene glycol at 80℃; for 3h; Suzuki coupling;	95%

5-bromo-2-aminopyrimidine (7752-82-1) + di-tert-butyl dicarbonate (24424-99-5) → 2-[bis(tert-butoxycarbonyl)amino]-5-bromopyrimidine (209959-33-1)

Conditions	Yield
With pyridine at 70℃;	93%
With pyridine at 70℃; for 16h;	93%
With dmap In tetrahydrofuran at 20℃; Inert atmosphere;	86%

5-bromo-2-aminopyrimidine (7752-82-1) + benzyl bromide (100-39-0) → 5-bromo-2-dibenzylaminopyrimidine (886366-28-5)

Conditions	Yield
Stage #1: 5-bromo-2-aminopyrimidine With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 0℃; for 2h; Inert atmosphere;	92%

Upstream product

• 109-12-6 2-aminopyrimidine 
• 35034-15-2 2‐aminopyrimidine‐1‐oxide 
• 7664-41-7 ammonia 
• 32779-36-5 5-Bromo-2-chloropyrimidine 
• 504-29-0 2-aminopyridine 

Downstream Products

• 38373-55-6 benzyl-(5-bromo-pyrimidin-2-yl)-amine 
• 91348-67-3 N-(5-bromopyrimidin-2-yl)-4-methylbenzenesulfonamide 
• 860515-93-1 3-nitro-benzenesulfonic acid-(5-bromo-pyrimidin-2-ylamide) 
• 132635-73-5 N-(5-Bromo-pyrimidin-2-yl)-2-methyl-benzamidine 
• 126556-14-7 1-Benzoyl-3-(5-bromo-pyrimidin-2-yl)-thiourea 
• 126556-15-8 1-(5-Bromo-pyrimidin-2-yl)-3-(4-methyl-benzoyl)-thiourea 
• 126556-16-9 1-(5-Bromo-pyrimidin-2-yl)-3-(4-methoxy-benzoyl)-thiourea 
• 120821-52-5 N-(5-Bromo-pyrimidin-2-yl)-4-methoxy-benzamide 
• 132635-74-6 N-(5-Bromo-pyrimidin-2-yl)-4-methyl-benzamidine 
• 218302-19-3 2-(6-amino-3-pyrimidinyl)benzene-tert-butylsulfonamide 
• 1753-48-6 2-aminopyrimidine-5-carbonitrile 
• 294895-76-4 1-(2-aminopyrimidin-5-yl)-2-(4-butylsulfanylphenyl)ethyne 
• 355398-02-6 6-bromo-2-phenyl-imidazo[1,2-a]pyrimidine 
• 335030-77-8 benzyl (E)-3-(2-aminopyrimidin-5-yl)acrylate 

Relevant articles and documents

Introducing a potential lead structure for the synthesis of more specific inhibitors of tyrosinases and catechol oxidases

Based on tyrosinase inhibition science, two pyrimidine derivatives were designed and studied. Docking of 2-dibenzylamine-5-hydroxy pyrimidine (dba5HP) and 2-benzylamino-5-hydroxy pyrimidine (ba5HP) on mushroom tyrosinase (MT) showed that the former could not occupy MT active site pocket, while ba5HP could do so (Moldock score = ? 63.95). MD simulation revealed that the complex of ba5HP-MT reached stability 50 = 32.28, Ki = 11.32?μM). Considering the facile synthesis, potential for structural modifications, and passing most of the lead-likeness filters, it seems likely that ba5HP plays key roles in the syntheses of novel depigmentation medicines as well as more specific inhibitors for various tyrosinases and polyphenol oxidases.

Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies

Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule, (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 μM) and displayed low affinity for hERG (IC50 > 40 μM). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies.

Proton Sensitive Functional Organic Fluorescent Dyes Based on Coumarin-imidazo[1,2-a]pyrimidine; Syntheses, Photophysical Properties, and Investigation of Protonation Ability

A novel series of 2-coumarin-3-yl-imidazo[1,2-a]pyrimidines have been synthesized with functionalized coumarin and pyrimidine units of the different architecture to give various fluorescent compounds. A new additional series bearing unsubstituted coumarin and 7-dialkylaminocoumarin as fluorophore were obtained by palladium-catalyzed cross-coupling reactions, through coupling of 6-bromo-2-coumarin-3-yl-imidazopyrimidine derivatives with various arylboronic acids. In the all reaction step, microwave irradiation (MWI) method was used and compared with the conventional method (CM). Photophysical properties of synthesized compounds were studied by a combination of UV/Vis and fluorescence spectroscopy in various solvents having different polarities. The protonation abilities of all compounds were investigated by titration with trifluoroacetic acid (TFA) in dichloromethane. In both series, the compounds bearing 7-dialkylaminocoumarin are fluorescently active even in daylight and showed maximum absorption wavelengths (λabs–max) in the visible region in all solvents used. In addition, they showed drastic color and emission change in acidic environment. Moreover, for the investigation of protonation ability of three selected compounds bearing 7-dialkylaminocoumarin have been studied using a buffer solution with various pH and determinated their pKa values. The compound bearing morpholine has the potential to use as colorimetric and luminescence pH sensor. The thermal properties of all the synthesized compounds were also evaluated with TGA to test their usability as optic dyes.

2-polysubstituted aromatic ring-pyrimidine derivative and preparation and medical application

The invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative, an optical isomer of the derivative or a medically acceptable salt or solvate of the derivative, and application of the compound, the optical isomer of the derivative or the medically acceptable salt or solvate of the derivative in preparing antineoplastic medicine. According to the 2-polysubstituted aromatic ring-pyrimidine derivative, by adopting N-substituted pyridine-2-minopyrimidine as a lead compound obtained based on virtual screening of a structure, a series of brand new small molecule Chk1 inhibitors are designed and synthesized, and a Chk1 kinase inhibitory activity test of a molecular level is conducted on the compound. Experiments prove that the compound is a Chk1 inhibitor with a strong antitumous effect, Chk1 kinase inhibitory activity and a prospect, and new cancer treating medicine, and can be used for treating solid tumor or leukemia related with human or animal cell proliferation. The 2-polysubstituted aromatic ring-pyrimidine derivative has a structure shown in the general formula I.

IF5 affects the final stage of the Cl-F exchange fluorination in the synthesis of pentafluoro-λ6-sulfanyl-pyridines, pyrimidines and benzenes with electron-withdrawing substituents

A difficult chlorine-fluorine (Cl-F) exchange fluorination reaction in the final stage of the preparation of pentafluoro-λ6-sulfanyl-(hetero)arenes having electron-withdrawing substituents has now been elucidated through the use of iodine pentafluoride. A major side-reaction of C-S bond cleavage was sufficiently inhibited by the potential interaction between F and I with a halogen bonding.

pyrimidine derivatives substituted with aryl- or heteroaryl- substituted fluorene group, and organic electroluminescent device including the same

Aryl group or a heteroaryl group substituted pyrimidine derivatives of formula 1 is coupled to polyarylenic backbone containing encoded ball number. [Formula 1] [In said formula 1, Ar1 And Ar2 Are each independently a hydrogen, methyl or phenyl, The C L6 - C24 C aryl of reflector3 - C24 It will be biting and heteroatoms, N is an integer 0 or 1 and, Ar3 The C6 - C30 C aryl of reflector3 - C30 A variety of printers] (by machine translation)

Synthesis method of 2-amino-5-bromopyrimidine

The invention relates to a synthesis method of 2-amino-5-bromopyrimidine. The 2-aminopyrimidine and N-bromo-succinimide are used as raw materials; the mol ratio of the 2-aminopyrimidine to the N-bromo-succinimide is 1: (0.65 to 2.3); the mol ratio of the 2-aminopyrimidine to a solvent is 1:(2.0 to 11); in a proper solvent, the reaction is continuously performed for 3 to 15 hours at 35 to 110 DEG C to produce a coarse product of 2-amino-5-bromopyrimidine; through recrystallization, a pure product of the 2-amino-5-bromopyrimidine is obtained. The raw materials can be easily obtained; the price is reasonable; meanwhile, heavy metal and corrosion gas are not used in the preparation reaction; the reaction is mild; no special requirements exist on the reaction equipment; the production can be performed by using ordinary anti-corrosion equipment; the reaction yield is high; the purity is high.

KINASE INHIBITOR AND USE THEREOF

The invention relates to a CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers; a pharmaceutical formulation, pharmaceutical composition and kit comprising said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers, and use of said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers. For example, the compounds of the invention are useful for reducing or inhibiting the activity of CDK4/6 kinase in a cell, and/or treating and/or preventing a cancer-related disease mediated by CDK4/6 kinase.

A quick, mild and efficient bromination using a CFBSA/KBr system

Bromination is a fundamental transformation in organic chemistry and brominated compounds as building blocks are of paramount importance in organic synthesis. In our study, we have developed an efficient method of bromination by using a CFBSA/KBr system at room temperature in a short reaction time. Notably, this approach has been proven to be applicable to a range of substrates including 1,3-diketones and β-keto esters, phenols, aromatic amines and heteroarenes with good to excellent yields.

Synthesis and biological evaluation of glucagon-like peptide-1 receptor agonists

In this study, a series of fused-heterocyclic derivatives were systematically designed and synthesized using an efficient route, and evaluated in terms of GLP-1R agonist activity. We employed short synthetic steps and reactions that are tolerant of the presence of various functional groups and suitable for parallel operations to enable the rapid generation of libraries of diverse and structurally complex small molecules. Of the compounds synthesized, 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a] pyridin-2-yl)phenyl methanesulfonate (8e) was the most potent agonist with an EC50 of 7.89 μM, and thus is the compound with the greatest potential for application. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1R agonists that can be administered orally.