31169-27-4

Usage

Uses

Used in Pharmaceutical Industry:
7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE is used as a chemical intermediate for the synthesis of various pharmaceuticals. Its unique structure and reactivity contribute to the development of new drugs with improved therapeutic properties.
Used in Agrochemical Industry:
7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE is used as a building block in the development of agrochemicals. Its incorporation into the molecular structure of these chemicals can enhance their effectiveness in agricultural applications.
Used in Materials Science:
7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE is used as a component in the research and development of advanced materials. Its unique structure and properties can contribute to the creation of new materials with specific characteristics for various applications.
Used in Organic Electronics:
7-BROMO-4-CHLOROTHIENO[3,2-D]PYRIMIDINE is used in the field of organic electronics due to its potential applications in the development of organic semiconductors, which can be used in various electronic devices and systems.

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

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

Downstream Products

• 272-68-4 thieno[3,2-d]pyrimidine 
• 16269-66-2 4-chlorothieno[3,2-d]pyrimidine 
• 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 
• 1446111-75-6 4-amino-N-(4-((4-chlorophenyl)amino)-7-methylquinazolin-8-yl)thieno[3,2-d]pyrimidine-7-carboxamide 
• 1446111-86-9 4-amino-N-(6-methyl-1-phenoxyisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide 
• 1446112-11-3 4-amino-N-(1-((4-chloro-3-((dimethylamino)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide 
• 1446112-26-0 4-amino-N-(6-methyl-1-((3-(methylsulfonamido)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide 

Relevant academic research and scientific papers

An Efficient Second-Generation Manufacturing Process for the pan-RAF Inhibitor Belvarafenib

Herein, the development of a streamlined manufacturing process for the pan-RAF inhibitor belvarafenib (GDC-5573) is reported. The process to belvarafenib features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access the penultimate intermediate 3. The final amide coupling was accomplished by a mild and safe protocol employing N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate as the coupling reagent, which afforded belvarafenib on a multikilogram production scale after recrystallization.

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.

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.

FUSED PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON FMS KINASES

Disclosed are a fused pyrimidine derivative of formula (I), and a pharmaceutically acceptable salt, stereoisomer, hydrate and solvate thereof, which have an excellent inhibitory activity on FMS kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating diseases caused by abnormal activation of FMS kinases such as immunologic diseases, metabolic diseases, inflammatory diseases, cancers and tumors.

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.

NOVEL PYRIMIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION INCLUDING SAME AS AN ACTIVE INGREDIENT

The present invention relates to a compound represented by formula (I) for inhibiting the activity of diacylglycerol O-acyltransferase type 1 (DGAT1), and pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention may be used effectively in the treatment or prevention of a disease or condition mediated by the activity of DGAT1 such as obesity, type II diabetes, dyslipidemia, metabolic syndrome, and the like, without any adverse effects: wherein A, B, X, and R5 to R7 are the same as defined in the specification.

NOVEL PYRIMIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION INCLUDING SAME AS AN ACTIVE INGREDIENT

The present invention relates to a compound represented by formula (I) for inhibiting the activity of diacylglycerol O-acyltransferase type 1 (DGAT1), and pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention may be used effectively in the treatment or prevention of a disease or condition mediated by the activity of DGAT1 such as obesity, type II diabetes, dyslipidemia, metabolic syndrome, and the like, without any adverse effects: wherein A, B, X, and R5 to R7 are the same as defined in the specification.

THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON PROTEIN KINASES

The present invention relates to a thieno[3,2-d]pyrimidine derivative of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, which has an excellent inhibitory activity on protein kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating abnormal cell growth diseases.

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

NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS

The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.