31169-27-4

Basic information

• Product Name: 7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE
• Synonyms: 7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE;7-Bromo-4-chlorothieno[3,...;Thieno[3,2-d]pyrimidine,7-bromo-4-chloro-;7-Bromo-4-chloro-1,2-dihydro-thieno[3,2-d]pyrimidine
• CAS NO: 31169-27-4
• Molecular Formula: C₆H₂BrClN₂S
• Molecular Weight: 249.52
• Product Categories: CHIRAL CHEMICALS;Heterocycle-Pyrimidine series
• Mol File: 31169-27-4.mol
• Article Data: 19

Chemical Properties

• Boiling Point: 345.453 °C at 760 mmHg
• Flash Point: 162.724 °C
• Appearance: /
• Density: 1.955 g/cm³
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: -0.77±0.40(Predicted)
• CAS DataBase Reference: 7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE(31169-27-4)
• EPA Substance Registry System: 7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE(31169-27-4)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN2811
• HazardClass: IRRITANT
• Hazardous Substances Data: 31169-27-4(Hazardous Substances Data)

Usage

General Description

7-Bromo-4-chlorothieno[3,2-d]pyrimidine is a chemical compound with the molecular formula C6H3BrClN2S. It is a heterocyclic compound that consists of a thiophene ring fused to a pyrimidine ring with chlorine and bromine substituents. 7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE is commonly used as an intermediate in the synthesis of pharmaceuticals and agrochemicals. It has the potential to be used as a building block for the development of new drugs and agricultural chemicals due to its unique structure and reactivity. Additionally, it has been studied for its potential applications in the field of materials science and organic electronics.

Synthetic route

7-bromo-4-(methylsulfanyl)thieno[3,2-d]pyrimidine (1246223-38-0) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
With sulfuryl dichloride In dichloromethane; acetonitrile at 0℃; for 0.5h;	99%

7-bromothieno[3,2-d]pyrimidine-4(3H)-one (31169-25-2) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
With trichlorophosphate for 2h; Heating / reflux;	95%
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 3h; Reflux;	85%
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 3h; Reflux;	85%

7-bromo-4-hydroxythienopyrimidine → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
With trichlorophosphate at 125℃; for 6h; Temperature; Time;	89%

aqueous sodium chloride + 7-bromothieno[3,2-d]pyrimidine-4(3H)-one (31169-25-2) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
With sodium hydrogencarbonate In trichlorophosphate	82%

3H-thieno[3,2-d]pyrimidin-4-one (16234-10-9) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + 7-bromothieno[3,2-d]pyrimidine-4(3H)-one (31169-25-2)

Conditions	Yield
With bromine; sodium hydrogencarbonate In acetic acid	A n/a B 64%

4-chlorothieno[3,2-d]pyrimidine (16269-66-2) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
With N-Bromosuccinimide; acetic acid In acetonitrile at 85℃; for 18h;	20%
With N-Bromosuccinimide; acetic acid In acetonitrile at 85℃; for 18h;

3H-thieno[3,2-d]pyrimidin-4-one (16234-10-9) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Br2 2: POCl3 View Scheme
Multi-step reaction with 2 steps 1: Br2 2: POCl3, Py View Scheme
Multi-step reaction with 2 steps 1: bromine / acetic acid / 10 h / 120 °C / sealed reactor 2: trichlorophosphate / 3 h / 150 °C View Scheme

Methyl 3-aminothiophene-2-carboxylate (22288-78-4) → 7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic anhydride 1.2: 3 h / 20 °C 1.3: 20 h / 20 - 150 °C 2.1: bromine / acetic acid / 18 h / 120 °C 3.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: 2-methoxy-ethanol / 4 h / 120 °C 2: sodium metaphposphate; N-Bromosuccinimide / acetone / 4 h / 15 °C 3: trichlorophosphate / 6 h / 125 °C View Scheme

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) → 7-bromothieno[3,2-d]pyrimidine-4-amine (1318133-32-2)

Conditions	Yield
With ammonia In isopropyl alcohol at 95 - 100℃; for 7h; Sealed tube;	97%
With ammonia In isopropyl alcohol at 95 - 100℃; for 7h; Sealed tube;	97%
With ammonia In isopropyl alcohol at 95 - 100℃; for 7h; Sealed tube;	97%
With ammonia In isopropyl alcohol at 100℃; for 12h; sealed vessel;	83%
With ammonia In isopropyl alcohol at 100℃; for 12h;	3.8 g

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + (R)-1-(4-chloro-2-(3-methyl-1H-pyrazole-1-yl)phenyl)-2,2,2-trifluoroethane-1-ol (1033805-26-3) → (R)-7-bromo-4-(1-(4-chloro-2-(3-methyl-1H-pyrazole-1-yl)phenyl)-2,2,2-trifluoroethoxy)thieno[3,2-d]pyrimidine

Conditions	Yield
Stage #1: (R)-1-(4-chloro-2-(3-methyl-1H-pyrazole-1-yl)phenyl)-2,2,2-trifluoroethane-1-ol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1h; Stage #2: 7-bromo-4-chlorothieno[3,2-d]pyrimidine In N,N-dimethyl-formamide; mineral oil at 20℃; for 12h;	96%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + tert-butylamine (75-64-9) → 7-bromo-N-(tert-butyl)thieno[3,2-d]pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 80℃;	95%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + sodium methylate (124-41-4) → 7-bromo-4-methoxythieno[3,2-d]pyrimidine (872190-91-5)

Conditions	Yield
In 1,4-dioxane at 20℃; for 12h; Inert atmosphere;	94%
In 1,4-dioxane at 20℃; for 18h; Inert atmosphere;	84%
In 1,4-dioxane at 20℃; for 12h;	53%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + (S)-1,3-dihydrospiro[indene-2,4′-piperidine]-1-amine dihydrochloride → (1S)-1'-(7-bromothieno[3,2-d]pyrimidin-4-yl)-1,3-dihydrospiro[indene-2,4'-piperidin]-1-amine

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 85℃; for 12h; Inert atmosphere;	94%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + 2,4-Dimethoxybenzylamine (20781-20-8) → 7-bromo-N-(2,4-dimethoxybenzyl)thieno[3,2-d]pyrimidine-4-amine (1527518-20-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;	89%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + phenol (108-95-2) → 7-bromo-4-phenoxythieno[3,2-d]pyrimidine

Conditions	Yield
With caesium carbonate In acetonitrile at 40℃; for 16h;	88%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + sodium tert-butyl thiolate (29364-29-2) → 7-bromo-4-tert-butylsulfanyl-thieno[3,2-d]pyrimidine (1370008-67-5)

Conditions	Yield
In dimethyl sulfoxide at 0 - 20℃; for 4h;	86%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + 3,5-dimethylphenyl boronic acid (172975-69-8) → 7-bromo-4-(3,5-dimethylphenyl)thieno[3,2-d]pyrimidine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 80℃; for 12h; Inert atmosphere;	75.2%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 80℃; for 12h; Inert atmosphere;	75.2%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) → (7-bromothieno[3,2-d]pyrimidin-4-yl)hydrazine hydrochloride (443762-07-0) + 3-pyridinecarboxaldehyde(7-bromothieno[3,2-d]pyrimidin-4-yl)hydrazone (443762-06-9)

Conditions	Yield
With hydrazine hydrate In ethanol	A 73% B n/a

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + sodium thiomethoxide (5188-07-8) → 7-bromo-4-(methylsulfanyl)thieno[3,2-d]pyrimidine (1246223-38-0)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 12h;	71%
In tetrahydrofuran at 0℃; for 15h;
In tetrahydrofuran at 0℃; for 15h;

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + (S)-1-Aminoindane (10277-74-4, 34698-41-4, 61341-86-4, 61949-83-5) → 7-bromo-N-[(1S)-indan-1-yl]thieno[3,2-d]pyrimidin-4-amine (1370007-92-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 100℃; for 3h; Microwave irradiation;	69%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + 4,4,5,5-tetramethyl-2-(4,9,9-trimethyl-9H-fluoren-2-yl)-1,3,2-dioxaborolane → 7-bromo-4-(4,9,9-trimethyl-9H-fluoren-2-yl)thieno[3,2-d]pyrimidine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water Inert atmosphere; Reflux;	67%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + 4-methylamino-piperidine-1-carboxylic acid tert-butyl ester (147539-41-1) → tert-butyl 4-((7-bromothieno[3,2-d]pyrimidin-4-yl)(methyl)amino)piperidine-1-carboxylate

Conditions	Yield
In dimethyl sulfoxide at 60℃;	58%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + tri-n-butyl(vinyl)tin (7486-35-3) → 4-chloro-7-vinylthieno[3,2-d]pyrimidine

Conditions	Yield
Stage #1: 7-bromo-4-chlorothieno[3,2-d]pyrimidine; tri-n-butyl(vinyl)tin With copper(l) iodide; bis(tri-t-butylphosphine)palladium(0) at 120℃; for 24h; Stille Cross Coupling; Inert atmosphere; Stage #2: With potassium fluoride In water at 20℃; for 0.25h;	50%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + potassium tert-butylate (865-47-4) → 7-bromo-4-(tert-butoxy)thieno[3,2-d]pyrimidine

Conditions	Yield
In tetrahydrofuran at 0℃; for 1.5h;	30.5%

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) → thieno[3,2-d]pyrimidine (272-68-4)

Conditions	Yield
With hydrogen; palladium on activated charcoal

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) → 7-bromo-4-hydrazino-thieno[3,2-d]pyrimidine (31169-29-6)

Conditions	Yield
With hydrazine hydrate

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) → 4-chlorothieno[3,2-d]pyrimidine (16269-66-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) → 7-bromo-thieno[3,2-d]pyrimidine (21586-25-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: N2H4*H2O 2: O2, NaOEt View Scheme

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + sodium hydrosulfide monohydrate → 7-Bromo-3,4-dihydrothieno[3,2-d]pyrimidin-4-thione (215928-51-1)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one In water; ethyl acetate

7-bromo-4-chlorothieno[3,2-d]pyrimidine (31169-27-4) + isopropylamine (75-31-0) → 7-bromo-N-isopropylthieno[3,2-d]pyrimidin-4-amine (1235035-76-3)

Conditions	Yield
In ethanol for 15h; Reflux;

Upstream product

• 16234-10-9 3H-thieno[3,2-d]pyrimidin-4-one 
• 31169-25-2 7-bromothieno[3,2-d]pyrimidine-4(3H)-one 
• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 
• 16269-66-2 4-chlorothieno[3,2-d]pyrimidine 
• 1246223-38-0 7-bromo-4-(methylsulfanyl)thieno[3,2-d]pyrimidine 

Downstream Products

• 1318133-32-2 7-bromothieno[3,2-d]pyrimidine-4-amine 
• 1318126-81-6 ethyl 3-((4-(cyclopropylamino)thieno[3,2-d]pyrimidine-7-yl)ethynyl)-4-methyl benzoate 
• 1318127-08-0 (E)-ethyl-3-(2-(4-aminothieno[3,2-d]pyrimidine-7-yl)vinyl)-4-methyl benzoate 
• 1318242-75-9 (E)-3-(2-(4-aminothieno[3,2-d]pyrimidine-7-yl)vinyl)-4-methylbenzoic acid 
• 1318241-43-8 (E)-3-(2-(4-aminothieno[3,2-d]pyrimidine-7-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide 
• 1352812-53-3 C₂₅H₂₅FN₄O₄S 
• 1352812-55-5 C₂₅H₂₃FN₄O₄S 
• 1352813-03-6 C₂₀H₁₇FN₄O₂S*ClH 

Relevant articles and documents

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Synthetic process of 7-bromo-4-chlorothieno [3,2-D] pyrimidine

The invention relates to a synthetic method of 7-bromo-4-chlorothieno [3,2-D] pyrimidine. The synthetic method comprises the following steps: adding 3-amino-2-methyl formate thiophene and formamide into ethylene glycol monomethyl ether, heating to 120-140 DEG C to reflux, then adding saturated salt water when a solvent is not reduced anymore, and filtering to obtain solid 4-hydroxyl thieno-pyrimidine; adding 4-hydroxyl thieno-pyrimidine, N-bromo-succinimide and sodium hexametahposphate into acetone, reacting at 5-30 DEG C, filtering, adding water into a filtrate, stirring, filtering, and collecting solids to obtain 4-hydroxyl-7-bromo-thieno-pyrimidine; and adding the 4-hydroxyl-7-bromo-thieno-pyrimidine into phosphorus oxychloride, heating to reflux, then pouring into ice water, stirring until solids are generated, filtering, and drying in the air to obtain 7-bromo-4-chlorothieno [3,2-D] pyrimidine. By use of the synthetic process, the total yield of the 7-bromo-4-chlorothieno [3,2-D] pyrimidine is improved, the cost is effectively reduced. The synthetic method of 7-bromo-4-chlorothieno [3,2-D] pyrimidine is suitable for industrial large-scale synthesis application.

THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES

Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.