Welcome to LookChem.com Sign In|Join Free

CAS

  • or

915087-33-1

Post Buying Request

915087-33-1 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

915087-33-1 Usage

Description

MDV-3100, also known as Enzalutamide, is a second-generation androgen receptor (AR) signaling inhibitor. It is a synthetic compound that blocks androgens from binding to the androgen receptor, preventing nuclear translocation and co-activator recruitment of the ligand-receptor complex. MDV-3100 has been shown to induce tumor cell apoptosis and has no agonist activity. It was approved by the US FDA in August 2012 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who have previously been treated with docetaxel.

Uses

Used in Prostate Cancer Treatment:
MDV-3100 is used as an androgen-receptor antagonist for the treatment of castration-resistant prostate cancer. It inhibits the binding of androgens to the androgen receptor, preventing the nuclear translocation and co-activator recruitment of the ligand-receptor complex, thereby blocking the growth of prostate cancer cells.
Used in Pharmaceutical Industry:
MDV-3100 is used as a second-generation androgen receptor signaling inhibitor in the development of drugs for the treatment of prostate cancer. Its potent inhibition of androgen binding, nuclear translocation, and association with DNA makes it a promising candidate for the development of new therapeutic agents in the pharmaceutical industry.

Pharmacological action

Enzalutamide (XTANDI) is an oral androgen receptor antagonist, which is approved by the current clinical research and the US FDA (Food and Drug Administration), for the development of post-chemotherapy metastatic castration tolerance of prostate cancer Treatment (i.e. patients with prostate cancer after chemotherapy, cancer or cancer cells are still growing in such patients), can extend the survival of patients. The incidence of prostate cancer in the United States is very high, with an annual increase of nearly 240,000 patients (the highest among all cancers), nearly 30,000 deaths every year (second only to lung cancer, breast cancer, colorectal cancer),but its incidence is low in China. Enzalutamide is an androgen receptor inhibitor, the target of action is different from the approved cabbitaxel in 2010 and the approved abbitolone in 2011, and can competitively inhibit androgen and receptor binding, and can inhibition of androgen receptor nuclear transport and the interaction of the receptor and DNA. Vitro studies have shown that enzalutamide can inhibit prostate cancer cell proliferation and induce death, and enzalutamide reduces tumor volume in mouse prostate cancer xenograft model experiment. The main metabolite of enzalutamide is N-demethylol enamine, which shows similar inhibitory activity with enzalutamide in vitro. The recommended adult dose for the drug is daily 160mg, rapidly absorbed after medication, plasma concentrations to reach the highest level in 0.5~3h, the average terminal half-life is 5.8d, the main metabolic enzymes are CYP2C8 and CYP3A4. The drug should be avoided with strong CYP2C8 inhibitors (such as gemfibrozil), if it is needed for co-administration, should reduce the dose of enzalutamide to 80mg, 1 day.

Treatment

In vitro, enzalutamide suppressed proliferation and induced apoptosis in human prostate cancer cell lines. The sensitivity of prostate cancer cells to T cell-mediated lysis via androgen receptor-dependent immunomodulation was enhanced by enzalutamide. Enzalutamide lacked androgen receptor agonist activity in CRPC cell models and induced tumour regression in CRPC xenograft models.

Indications

For the treatment of metastatic or recurrence of advanced male castration tolerance of prostate cancer.

Clinical evaluation

Enzalutamide is an oral androgen receptor inhibitor that reduces the risk of radiation-related disease progression and death. Although anti-androgen therapy has been the preferred treatment option for patients with metastatic prostate cancer for more than 70 years, researchers have found that male hormone receptors play an important role in the development of prostate cancer throughout the course of disease with the in-depth exploration of disease at the molecular level. FDA-approved new generation of androgen receptor antagonists such as abiraterone and enzolatamide have shown that it is benefit for patients with advanced prostate cancer after chemotherapy with docetaxel. Astellas in Japan and Johnson in the United States treat prostate cancer both through the target, according to statistics, similar to the treatment results, only a few differences, such as: abitron to be used simultaneously with steroid drugs , and enzalutamide is not required; abitron need to limit the diet, and enzalutamide does not need. Drugs in different countries is not the same as different the crowd, so there are price differences, but the effect is the same. This information was compiled by the Editor of the lookchem (2015-09-20).

Side effects

The main side effects of enxtran (XTANDI) are hypertension and fatigue. The most common adverse reactions (≥ 5%) are weakness/fatigue, back pain, diarrhea, joint pain, hot flashes, peripheral blood edema, musculoskeletal pain, headache, upper respiratory tract infection, muscle weakness, dizziness, insomnia, lower respiratory tract infection, spinal cord compression syndrome and cauda equina syndrome, hematuria, paresthesia, anxiety and hypertension.

Biological activity

Enzalutamide (MDV3100) is an androgen receptor (AR) antagonist with an IC50 of 36 nM. Enzalutamide is an androgen receptor (AR) antagonist with an IC50 of 36 nM in vitro studies. In competitive experiments with 16β-[18F] fluoro-5α-DHT (18-FDHT), enzalutamide was found to have higher affinity for bilirubin than Bicalutamide when administered to AR. While enzalutamide had no effect on LNCaP/AR (AR-overexpression) of prostate cells. In parental LNCaP cells, Enzalutamide inhibits the production of prostate specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2), and inhibits their binding to the synthetic and rogen R1881. Enzalutamide inhibits the translation activity of the mutant AR protein (W741C, Trp at position 741 mutanting to Cys). MDV310 also blocked the nuclear translocation and coordination receptor complexes that recruit coactivators.

In vivo studies

Enzalutamide treatment of castrated male mice carrying LNCa/AR xenografts, mice treated with 10 mg MDV310 per kilogram of body weight, can induce significant tumor regression.

Originator

University of California (United States)

Clinical Use

In August 2012, the FDA approved enzalutamide, marketed by Medivation and Astellas Pharma US for the treatment of metastatic castration-resistant prostate cancer (CRPC), specifically for those patients who had previously received docetaxel. Enzalutamide is an inhibitor of androgen receptors (AR)— whose increased expression has been closely linked with castration-resistant prostate cancer (CRPC),thus, AR inhibitors have seen increased recent attention from the medicinal chemistry community. Phase I/II trials were particularly promising for enzalutamide, as 43% of patients showed >50% sustained suppression of a key serum biomarker.

Synthesis

Of the several patents and papers describing synthetic approaches, a 2011 patent represents the most likely scale production route to enzalutamide, and this is described in the scheme.Commercially available carboxylic acid 70 was first converted to the corresponding acid chloride 71, followed by amide formation with methylamine to furnish benzamide 72 in 90% yield over two steps. Bromide 72 was then coupled with amine 73 using copper (I) catalysis to afford trisubstituted benzene 74 in 76% isolated yield. Esterification of 74 to 75 with iodomethane furnished one fragment for the key ring-forming event. Isothiocyanate 76, available in one step from the corresponding aniline 77, was then exposed to aminoester 75 in the presence of warm isopropyl acetate, resulting in construction of the lynchpin thiohydantoin and delivering enzalutamide (XI) in an impressive 78% yield. This 5-step process has successfully generated multi-gram quantities of the drug in 50.7% overall yield.

Drug interactions

Potentially hazardous interactions with other drugs Anticoagulants: possibly reduces concentration effect of coumarinsAnxiolytics: concentration of midazolam reduced.Cytotoxics: concentration of palbociclib possibly reduced - avoid. Lipid-regulating drugs: concentration increased by gemfibrozil - avoid or halve enzalutamide dose.

Metabolism

Clearance of enzalutamide is mainly via hepatic metabolism, producing an active metabolite that is equally as active as enzalutamide and circulates at approximately the same plasma concentration as enzalutamide. Under conditions of clinical use, enzalutamide is a strong inducer of CYP3A4, a moderate inducer of CYP2C9 and CYP2C19, and has no clinically relevant effect on CYP2C8Excreted mainly as metabolites 71% in urine and 14% via faeces.

References

Tran et al. (2009), Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer; Science 324 787 Jung et al. (2010), Structure-Activity Relationship for Thiohydantoin Androgen Receptor Antagonist for Castration-Resistant Prostate Cancer (CRPC); J. Med. Chem. 53 2779

Check Digit Verification of cas no

The CAS Registry Mumber 915087-33-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,1,5,0,8 and 7 respectively; the second part has 2 digits, 3 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 915087-33:
(8*9)+(7*1)+(6*5)+(5*0)+(4*8)+(3*7)+(2*3)+(1*3)=171
171 % 10 = 1
So 915087-33-1 is a valid CAS Registry Number.
InChI:InChI=1/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30)

915087-33-1SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 18, 2017

Revision Date: Aug 18, 2017

1.Identification

1.1 GHS Product identifier

Product name enzalutamide

1.2 Other means of identification

Product number -
Other names [14C]-Enzalutamide

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:915087-33-1 SDS

915087-33-1Synthetic route

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate allyl

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate allyl

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In dimethyl sulfoxide at 80℃; for 4h; Concentration; Temperature; Edman Degradation;90.9%
In Isopropyl acetate at 75 - 85℃; for 8h;557 g
2-methoxyethyl 2-{[3-fluoro-4-(methylcarbamoyl)phenyl]amino}-2-methylpropanoate

2-methoxyethyl 2-{[3-fluoro-4-(methylcarbamoyl)phenyl]amino}-2-methylpropanoate

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In Isopropyl acetate; dimethyl sulfoxide at 85℃; for 16h;90.3%
4-bromo-2-fluoro-N-methylbenzanamide
749927-69-3

4-bromo-2-fluoro-N-methylbenzanamide

2-(trifluoromethyl)-4-(4,4-dimethyl 5-oxo-2-thioimidazolin-1-yl)benzonitrile
143782-28-9

2-(trifluoromethyl)-4-(4,4-dimethyl 5-oxo-2-thioimidazolin-1-yl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
With copper(l) iodide; 2-acetylcyclohexanone; potassium carbonate In N,N-dimethyl-formamide at 110℃; for 22h; Inert atmosphere;88.7%
Stage #1: 2-(trifluoromethyl)-4-(4,4-dimethyl 5-oxo-2-thioimidazolin-1-yl)benzonitrile With sodium hydride In N,N-dimethyl-formamide at 0 - 5℃; for 0.5h;
Stage #2: 4-bromo-2-fluoro-N-methylbenzanamide In N,N-dimethyl-formamide at 0 - 20℃; for 5h;
87.3%
2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methyl propanoic acid
1289942-66-0

2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methyl propanoic acid

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Stage #1: 2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methyl propanoic acid With triethylamine In dichloromethane; toluene at 30℃; for 0.166667h;
Stage #2: 4-isothiocyanato 2-(trifluoromethyl)benzonitrile In toluene at 50 - 60℃; for 4h; Temperature; Solvent;
88.5%
With N-ethyl-N,N-diisopropylamine; phenol at 60℃; for 4h; Reagent/catalyst;77%
Stage #1: 4-isothiocyanato 2-(trifluoromethyl)benzonitrile With triethylamine In chloroform at 20℃; for 0.25h; Reflux; Inert atmosphere;
Stage #2: 2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methyl propanoic acid In chloroform for 6h; Reagent/catalyst; Reflux;
76.92%
4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorobenzoic acid methyl ester

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorobenzoic acid methyl ester

methylamine
74-89-5

methylamine

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In tetrahydrofuran; water at -13℃; for 5h;88.18%
In toluene at 50℃; for 0.5h; Solvent; Temperature;86%
In tetrahydrofuran; water at -11 - -7℃; for 22.6667h; Temperature; Large scale;83.6%
ethyl N-[3-fluoro-4-(methylcarbamoyl)phenyl]-2-methylalaninate

ethyl N-[3-fluoro-4-(methylcarbamoyl)phenyl]-2-methylalaninate

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In Isopropyl acetate; dimethyl sulfoxide at 80℃; for 6h; Temperature;88%
With Isopropyl acetate In dimethyl sulfoxide at 90 - 95℃;0.2 g
In Isopropyl acetate; dimethyl sulfoxide at 90 - 95℃;0.2 g
2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate benzyl

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate benzyl

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In Isopropyl acetate; dimethyl sulfoxide at 85℃; for 6h; Temperature;88%
In dimethyl sulfoxide at 84℃; for 4h; Edman Degradation;86%
With copper(l) iodide; potassium carbonate In dimethyl sulfoxide at 80℃; Bucherer-Bergs Reaction; Inert atmosphere;309 g
2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropanoic acid methyl ester
1332524-01-2

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropanoic acid methyl ester

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In Isopropyl acetate; dimethyl sulfoxide at 70℃; for 6h; Temperature;85%
In Isopropyl acetate; dimethyl sulfoxide at 83 - 84℃; for 17.5h;82%
In Isopropyl acetate; dimethyl sulfoxide at 55 - 85℃; Inert atmosphere;80.2%
2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate ethyloxirane

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate ethyloxirane

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Edman Degradation;85%
C20H23FN2O4

C20H23FN2O4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In Isopropyl acetate; dimethyl sulfoxide at 80 - 85℃;83%
2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate proparagyl

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate proparagyl

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In dimethyl sulfoxide at 84℃; for 4h; Concentration; Temperature; Edman Degradation;82%
C16H23FN2O4

C16H23FN2O4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In Isopropyl acetate; dimethyl sulfoxide at 80 - 85℃; for 20h;82%
methyl 2-chloroisobutyrate
22421-97-2

methyl 2-chloroisobutyrate

N-(3-trifluoromethyl-4-cyanophenyl)-N'-(3-fluoro-4-methylcarbamoylphenyl)thiourea

N-(3-trifluoromethyl-4-cyanophenyl)-N'-(3-fluoro-4-methylcarbamoylphenyl)thiourea

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
With triethylamine In N,N-dimethyl-formamide at 80 - 90℃; for 5h;66.4%
C14H20FN3O2

C14H20FN3O2

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
In acetonitrile at 20 - 70℃; for 64h; Molecular sieve; Inert atmosphere;47.3%
N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide
915087-32-0

N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide

thiophosgene
463-71-8

thiophosgene

4-amino-2-trifluoromethylbenzonitrile
654-70-6

4-amino-2-trifluoromethylbenzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Stage #1: N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide; thiophosgene; 4-amino-2-trifluoromethylbenzonitrile In N,N-dimethyl acetamide at 0 - 60℃; Inert atmosphere;
Stage #2: With hydrogenchloride In methanol; N,N-dimethyl acetamide for 2h; Inert atmosphere; Reflux;
41%
N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide
915087-32-0

N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide

4-isothiocyanato 2-(trifluoromethyl)benzonitrile
143782-23-4

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Stage #1: N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide; 4-isothiocyanato 2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide at 100℃; for 11h; Microwave irradiation;
Stage #2: With hydrogenchloride In methanol; N,N-dimethyl-formamide for 1.5h; Heating / reflux;
25%
Stage #1: N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide; 4-isothiocyanato 2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide at 100℃; for 11h; Microwave irradiation;
Stage #2: With hydrogenchloride; methanol In water; N,N-dimethyl-formamide for 1h; Reflux;
23.1%
Stage #1: N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide; 4-isothiocyanato 2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide at 120℃; for 16h;
Stage #2: With hydrogenchloride; water In ethanol; N,N-dimethyl-formamide for 1h; Reflux;
17.1%
4-[1-(4-cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide
1289942-55-7

4-[1-(4-cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
With dmap; thiophosgene In acetonitrile at 40 - 60℃; for 24h; Solvent; Reagent/catalyst; Temperature; Inert atmosphere;19.1%
thiophosgene
463-71-8

thiophosgene

4-[1-(4-cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide
1289942-55-7

4-[1-(4-cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
at 100℃; for 6h; a sealed-tube;4%
at 100℃; for 6h; Sealed tube;1.5%
C21H17F4N5OS

C21H17F4N5OS

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
With hydrogenchloride; water In methanol; N,N-dimethyl-formamide for 1.5h; Heating / reflux;
With hydrogenchloride; water In methanol; N,N-dimethyl-formamide for 1.5h; Reflux; Inert atmosphere;30 mg
2-fluoro-4-bromobenzoic acid
112704-79-7

2-fluoro-4-bromobenzoic acid

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: thionyl chloride / N,N-dimethyl-formamide; Isopropyl acetate / 4.58 h / 21 - 72 °C / Inert atmosphere; Industry scale
2.1: water; Isopropyl acetate / 1.08 h / 2 - 35 °C / Inert atmosphere; Industry scale
3.1: potassium carbonate / copper(l) chloride / N,N-dimethyl-formamide; water / 30 °C
3.2: 105 °C / Inert atmosphere
3.3: pH 4
4.1: potassium carbonate / N,N-dimethyl-formamide; water / 30 °C
4.2: 1.08 h / 32 - 40 °C
5.1: dimethyl sulfoxide; Isopropyl acetate / 17.5 h / 83 - 84 °C
View Scheme
Multi-step reaction with 5 steps
1.1: thionyl chloride / N,N-dimethyl-formamide; Isopropyl acetate / 4.58 h / 21 - 72 °C / Inert atmosphere; Industry scale
2.1: water; Isopropyl acetate / 1.08 h / 2 - 35 °C / Inert atmosphere; Industry scale
3.1: potassium carbonate / copper(l) chloride / N,N-dimethyl-formamide; water / 30 °C
3.2: 105 °C / Inert atmosphere
3.3: pH 4
4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C
5.1: 6 h / 100 °C / a sealed-tube
View Scheme
Multi-step reaction with 4 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 10 - 30 °C
2.1: water; tert-butyl methyl ether / 10 - 30 °C / pH 8 - 9
3.1: potassium carbonate / N,N-dimethyl-formamide; 1,4-dioxane; water / 0.33 h / Inert atmosphere
3.2: 24.33 h / Inert atmosphere; Reflux
4.1: triethylamine / dichloromethane / 23 - 28 °C / Inert atmosphere
View Scheme
4-bromo-2-fluorobenzoyl chloride
151982-51-3

4-bromo-2-fluorobenzoyl chloride

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: water; Isopropyl acetate / 1.08 h / 2 - 35 °C / Inert atmosphere; Industry scale
2.1: potassium carbonate / copper(l) chloride / N,N-dimethyl-formamide; water / 30 °C
2.2: 105 °C / Inert atmosphere
2.3: pH 4
3.1: potassium carbonate / N,N-dimethyl-formamide; water / 30 °C
3.2: 1.08 h / 32 - 40 °C
4.1: dimethyl sulfoxide; Isopropyl acetate / 17.5 h / 83 - 84 °C
View Scheme
Multi-step reaction with 4 steps
1.1: water; Isopropyl acetate / 1.08 h / 2 - 35 °C / Inert atmosphere; Industry scale
2.1: potassium carbonate / copper(l) chloride / N,N-dimethyl-formamide; water / 30 °C
2.2: 105 °C / Inert atmosphere
2.3: pH 4
3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C
4.1: 6 h / 100 °C / a sealed-tube
View Scheme
Multi-step reaction with 3 steps
1.1: water; tert-butyl methyl ether / 10 - 30 °C / pH 8 - 9
2.1: potassium carbonate / N,N-dimethyl-formamide; 1,4-dioxane; water / 0.33 h / Inert atmosphere
2.2: 24.33 h / Inert atmosphere; Reflux
3.1: triethylamine / dichloromethane / 23 - 28 °C / Inert atmosphere
View Scheme
4-amino-2-trifluoromethylbenzonitrile
654-70-6

4-amino-2-trifluoromethylbenzonitrile

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: n-heptane; water / 16.5 h / 5 - 46.4 °C / Industry scale; Inert atmosphere
2: dimethyl sulfoxide; Isopropyl acetate / 17.5 h / 83 - 84 °C
View Scheme
Multi-step reaction with 2 steps
1.1: water / 1 h / 20 °C
2.1: N,N-dimethyl-formamide / 16 h / 120 °C
2.2: 1 h / Reflux
View Scheme
Multi-step reaction with 2 steps
1.1: dichloromethane; water / 0.25 h / 20 - 30 °C / Inert atmosphere
1.2: 4 h
2.1: triethylamine / chloroform / 0.25 h / 20 °C / Reflux; Inert atmosphere
2.2: 6 h / Reflux
View Scheme
4-bromo-2-fluoro-N-methylbenzanamide
749927-69-3

4-bromo-2-fluoro-N-methylbenzanamide

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1.1: potassium carbonate / copper(l) chloride / N,N-dimethyl-formamide; water / 30 °C
1.2: 105 °C / Inert atmosphere
1.3: pH 4
2.1: potassium carbonate / N,N-dimethyl-formamide; water / 30 °C
2.2: 1.08 h / 32 - 40 °C
3.1: dimethyl sulfoxide; Isopropyl acetate / 17.5 h / 83 - 84 °C
View Scheme
Multi-step reaction with 3 steps
1.1: potassium carbonate / copper(l) chloride / N,N-dimethyl-formamide; water / 30 °C
1.2: 105 °C / Inert atmosphere
1.3: pH 4
2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C
3.1: 6 h / 100 °C / a sealed-tube
View Scheme
Multi-step reaction with 2 steps
1.1: potassium carbonate / N,N-dimethyl-formamide; 1,4-dioxane; water / 0.33 h / Inert atmosphere
1.2: 24.33 h / Inert atmosphere; Reflux
2.1: triethylamine / dichloromethane / 23 - 28 °C / Inert atmosphere
View Scheme
2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methyl propanoic acid
1289942-66-0

2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methyl propanoic acid

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: potassium carbonate / N,N-dimethyl-formamide; water / 30 °C
1.2: 1.08 h / 32 - 40 °C
2.1: dimethyl sulfoxide; Isopropyl acetate / 17.5 h / 83 - 84 °C
View Scheme
Multi-step reaction with 2 steps
1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C
2: 6 h / 100 °C / a sealed-tube
View Scheme
Multi-step reaction with 2 steps
1: potassium carbonate / N,N-dimethyl-formamide / 10 h / 50 °C
2: dimethyl sulfoxide / 4 h / 84 °C
View Scheme
2-fluoro-4-nitrobenzoic acid
403-24-7

2-fluoro-4-nitrobenzoic acid

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: 1,1'-carbonyldiimidazole / dichloromethane / 1 h / 20 °C
1.2: 1 h
2.1: acetic acid; iron / ethyl acetate / 16 h / Reflux
3.1: acetic acid / 16 h / 80 °C / Sealed tube
4.1: N,N-dimethyl-formamide / 16 h / 120 °C
4.2: 1 h / Reflux
View Scheme
Multi-step reaction with 4 steps
1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 5.5 h / 0 - 25 °C
2: palladium 10% on activated carbon; hydrogen / methanol / 27 °C / 1500.15 - 1875.19 Torr
3: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / tetrahydrofuran / 8 h / 80 - 85 °C
4: Isopropyl acetate / dimethyl sulfoxide / 90 - 95 °C
View Scheme
Multi-step reaction with 5 steps
1.1: N,N-dimethyl-formamide; thionyl chloride / Isopropyl acetate / 60 °C / Inert atmosphere
2.1: Isopropyl acetate / 5 h / Inert atmosphere
3.1: hydrogen; palladium 10% on activated carbon / methanol / 1 h / 50 °C / 4500.45 Torr / Autoclave
3.2: Heating
4.1: triethylamine / N,N-dimethyl acetamide / 1 h / 70 °C
4.2: 1.67 h / 100 °C
5.1: N-ethyl-N,N-diisopropylamine; phenol / 4 h / 60 °C
View Scheme
2-fluoro-N-methyl-4-nitro-benzamide
915087-24-0

2-fluoro-N-methyl-4-nitro-benzamide

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1.1: acetic acid; iron / ethyl acetate / 16 h / Reflux
2.1: acetic acid / 16 h / 80 °C / Sealed tube
3.1: N,N-dimethyl-formamide / 16 h / 120 °C
3.2: 1 h / Reflux
View Scheme
Multi-step reaction with 3 steps
1: palladium 10% on activated carbon; hydrogen / methanol / 27 °C / 1500.15 - 1875.19 Torr
2: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / tetrahydrofuran / 8 h / 80 - 85 °C
3: Isopropyl acetate / dimethyl sulfoxide / 90 - 95 °C
View Scheme
Multi-step reaction with 3 steps
1.1: hydrogen; palladium 10% on activated carbon / methanol / 1 h / 50 °C / 4500.45 Torr / Autoclave
1.2: Heating
2.1: triethylamine / N,N-dimethyl acetamide / 1 h / 70 °C
2.2: 1.67 h / 100 °C
3.1: N-ethyl-N,N-diisopropylamine; phenol / 4 h / 60 °C
View Scheme
2-fluoro-N-methyl-4-amino-benzamide
915087-25-1

2-fluoro-N-methyl-4-amino-benzamide

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: acetic acid / 16 h / 80 °C / Sealed tube
2.1: N,N-dimethyl-formamide / 16 h / 120 °C
2.2: 1 h / Reflux
View Scheme
Multi-step reaction with 2 steps
1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / tetrahydrofuran / 8 h / 80 - 85 °C
2: Isopropyl acetate / dimethyl sulfoxide / 90 - 95 °C
View Scheme
Multi-step reaction with 2 steps
1: acetic acid / acetone / 85 °C
2: pyridine / 60 - 90 °C
View Scheme
2-fluoro-4-nitrotoluene
1427-07-2

2-fluoro-4-nitrotoluene

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: sodium bromide; sulfuric acid / water / 80 - 85 °C
1.2: 27 h / 80 - 85 °C
2.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 5.5 h / 0 - 25 °C
3.1: palladium 10% on activated carbon; hydrogen / methanol / 27 °C / 1500.15 - 1875.19 Torr
4.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / tetrahydrofuran / 8 h / 80 - 85 °C
5.1: Isopropyl acetate / dimethyl sulfoxide / 90 - 95 °C
View Scheme
Multi-step reaction with 5 steps
1.1: periodic acid; chromium(VI) oxide / acetonitrile / 1 h
2.1: thionyl chloride / N,N-dimethyl-formamide / 1 h / -5 °C
2.2: 1 h
3.1: acetic acid; iron / ethyl acetate / 1 h / Reflux
4.1: magnesium sulfate / 12 h / 80 °C
5.1: N,N-dimethyl acetamide / 100 °C
5.2: 1.5 h / Reflux
View Scheme
4-amino-2-fluoro-N-methylbenzamide hydrochloride

4-amino-2-fluoro-N-methylbenzamide hydrochloride

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: triethylamine / N,N-dimethyl acetamide / 1 h / 70 °C
1.2: 1.67 h / 100 °C
2.1: N-ethyl-N,N-diisopropylamine; phenol / 4 h / 60 °C
View Scheme
2-fluoro-4-nitrobenzoyl chloride
403-23-6

2-fluoro-4-nitrobenzoyl chloride

enzalutamide
915087-33-1

enzalutamide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: Isopropyl acetate / 5 h / Inert atmosphere
2.1: hydrogen; palladium 10% on activated carbon / methanol / 1 h / 50 °C / 4500.45 Torr / Autoclave
2.2: Heating
3.1: triethylamine / N,N-dimethyl acetamide / 1 h / 70 °C
3.2: 1.67 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; phenol / 4 h / 60 °C
View Scheme
enzalutamide
915087-33-1

enzalutamide

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-imidazolidinethione-1-yl)-2-fluorobenzoic acid
1242137-15-0

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-imidazolidinethione-1-yl)-2-fluorobenzoic acid

Conditions
ConditionsYield
With hydrogenchloride In 1,4-dioxane for 2h; Reflux;95%
With hydrogenchloride In 1,4-dioxane; water for 2h; Reflux;95%
With hydrogenchloride In water at 120℃; for 48h; Pressure vessel;
With hydrogenchloride In water at 120℃; for 48h;
enzalutamide
915087-33-1

enzalutamide

di-tert-butyl dicarbonate
24424-99-5

di-tert-butyl dicarbonate

t-butyl (4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluorophenyl)(methyl)formamide

t-butyl (4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluorophenyl)(methyl)formamide

Conditions
ConditionsYield
With dmap In dichloromethane at 25℃; for 12h;92.3%
enzalutamide
915087-33-1

enzalutamide

tetramethylammonium fluoride
373-68-2

tetramethylammonium fluoride

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N,N-dimethylbenzamide

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N,N-dimethylbenzamide

Conditions
ConditionsYield
In toluene at 100℃; for 12h;53%
enzalutamide
915087-33-1

enzalutamide

4-(3-(4-cyano-3-(difluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide

4-(3-(4-cyano-3-(difluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide

Conditions
ConditionsYield
With 2,2,6,6-tetramethyl-piperidine; 1,2,2,6,6-pentamethylpiperidine; 4-sulfanylphenol; 1,3-dicyano-2,4,5,6-tetrakis(N,N-diphenylamino)-benzene In 1,2-dichloro-ethane at 25℃; for 12h; Sealed tube; Irradiation; Inert atmosphere;40%
enzalutamide
915087-33-1

enzalutamide

bis(trichloromethyl) carbonate
32315-10-9

bis(trichloromethyl) carbonate

isopropyl (2S)-2-[[[4-(hydroxymethyl)phenoxy](methoxymethyl)phosphoryl]amino]propanoate

isopropyl (2S)-2-[[[4-(hydroxymethyl)phenoxy](methoxymethyl)phosphoryl]amino]propanoate

isopropyl (2S)-2-[[[4-[[[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]-2-fluorobenzoyl]-methylcarbamoyl]oxymethyl]phenoxy](methoxymethyl)phosphoryl]amino]propanoate

isopropyl (2S)-2-[[[4-[[[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]-2-fluorobenzoyl]-methylcarbamoyl]oxymethyl]phenoxy](methoxymethyl)phosphoryl]amino]propanoate

Conditions
ConditionsYield
Stage #1: enzalutamide With chloro-trimethyl-silane; triethylamine In tetrahydrofuran at 60℃; for 0.5h; Cooling with ice;
Stage #2: bis(trichloromethyl) carbonate In tetrahydrofuran at 60℃; for 2h;
Stage #3: isopropyl (2S)-2-[[[4-(hydroxymethyl)phenoxy](methoxymethyl)phosphoryl]amino]propanoate With dmap In tetrahydrofuran at 20℃; for 1h; Cooling with ice;
27.76%
enzalutamide
915087-33-1

enzalutamide

2(13)CN(1-)*Zn(2+)

2(13)CN(1-)*Zn(2+)

C21(13)CH19F3N4O2S

C21(13)CH19F3N4O2S

Conditions
ConditionsYield
With C10H12O2NiC8H12-1,5-cyclo; triphenylborane; diphenyl(methyl)phosphine In 1-methyl-pyrrolidin-2-one at 100℃; for 18h; Inert atmosphere; Glovebox; Sealed tube;13%
enzalutamide
915087-33-1

enzalutamide

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide
1242137-18-3

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide

Conditions
ConditionsYield
With dihydrogen peroxide In ethanol; water for 1h; Reflux;

915087-33-1Relevant articles and documents

Synthesis method of enzalutamide

-

, (2021/04/14)

The invention discloses a synthesis method of enzalutamide. According to the method, 4-amino-2-trifluoromethyl benzonitrile is adopted as an initial raw material, and the initial raw material, benzoyl isothiocyanate (a reaction product of ammonium thiocyanate and benzoyl chloride), methyl 2-methyl-2-chloropropionate and N-methyl-4-bromo-2-fluorobenzamide are sequentially subjected to a multi-step substitution reaction to obtain the enzalutamide. The synthesis method not only can guarantee the yield and the product quality, but also can protect the health and safety of personnel, is safe in production, and is suitable for industrial production.

Preparation method of enzalutamide intermediate

-

, (2020/07/13)

The invention provides a preparation method of an enzalutamide intermediate (formula A). The R group is selected from C1-C4 alkyl, benzyl and phenyl groups, an intermediate (formula A) is synthesizedthrough the method and used for preparing enzalutamide, the reagents such as halogenated hydrocarbon with high toxicity are prevented for producing enzalutamide, meanwhile, by-product impurities generated due to use of inorganic base are avoided, and the yield and purity are high.

PROCESS FOR PREPARATION OF ENZALUTAMIDE

-

, (2021/01/23)

The presented invention relates to a process for preparation of Enzalutamide, compound (1) or a salt or a solvate thereof Formula (1). The presented invention also related to 1,4-dioxane solvate of compound (1).

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 915087-33-1