403-24-7

Usage

Chemical Properties

white to light yellow crystal powder

InChI:InChI=1/C7H4FNO4/c8-6-3-4(9(12)13)1-2-5(6)7(10)11/h1-3H,(H,10,11)/p-1

Synthetic route

2-fluoro-4-nitrotoluene (1427-07-2) → 2-fluoro-4-nitrobenzoic acid (403-24-7)

Conditions	Yield
With chromium(VI) oxide; periodic acid In acetonitrile for 1h;	81%
With chromium(VI) oxide; periodic acid In acetonitrile for 1h;	81%
With chromium(VI) oxide; periodic acid In acetonitrile for 1h; Inert atmosphere;	81%

1-(2-fluoro-4-nitrophenyl)ethanone (866579-96-6) → 2-fluoro-4-nitrobenzoic acid (403-24-7)

Conditions	Yield
With copper (II) nitrate tetrahydrate; oxygen In acetonitrile at 180℃; under 18751.9 Torr; for 1.5h; Green chemistry;	69%

2-fluoro-4-nitrotoluene (1427-07-2) + acetic acid (64-19-7) → 2-fluoro-4-nitrobenzoic acid (403-24-7)

Conditions	Yield
With potassium dichromate; sulfuric acid at 90℃; for 3h;	62%

2-fluoro-4-nitrobenzoic acid (403-24-7) → 2-fluoro-4-aminobenzoic acid (446-31-1)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate at 20℃; under 760 Torr;	100%
With hydrogen; palladium over charcoal In methanol; acetic acid at 20℃; under 760.051 Torr;	100%
With hydrogen; palladium 10% on activated carbon In methanol	100%
With ammonium hydroxide; iron(II) sulfate
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 16h;

2-fluoro-4-nitrobenzoic acid (403-24-7) → 2-fluoro-4-nitrobenzoyl chloride (403-23-6)

Conditions	Yield
With thionyl chloride at 80℃; for 3h;	100%
With thionyl chloride In toluene for 3h; Heating;	86%
With thionyl chloride

2-fluoro-4-nitrobenzoic acid (403-24-7) + diazomethyl-trimethyl-silane (18107-18-1) → 2-fluoro-4-nitro-benzoic acid methyl ester (392-09-6)

Conditions	Yield
In methanol; diethyl ether; toluene at 20℃; for 1.5h;	100%
In methanol

2-fluoro-4-nitrobenzoic acid (403-24-7) + N-(tert-butyl)oxycarbonyl-N,N’-trimethyl-1,3-diaminopropane (123183-72-2) → tert-Butyl (3-{[(2-fluoro-4-nitrophenyl)carbonyl](methyl)amino}propyl)methylcarbamate (1246246-94-5)

Conditions	Yield
Stage #1: 2-fluoro-4-nitrobenzoic acid With pivaloyl chloride; triethylamine In dichloromethane at 20℃; for 0.25h; Cooling with ice; Stage #2: N-(tert-butyl)oxycarbonyl-N,N’-trimethyl-1,3-diaminopropane In dichloromethane at 20℃; for 2h; Cooling with ice;	100%

2-fluoro-4-nitrobenzoic acid (403-24-7) + 5-chloro-4-(1-(phenylsulfonyl)-1-indol-3-yl)-N-(piperidin-4-yl)pyrimidin-2-amine → (4-(5-chloro-4-(1-(phenylsulfonyl)-1H-indol-3-yl)pyrimidin-2-ylamino)piperidin-1-yl)(2-fluoro-4-nitrophenyl)methanone

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 23℃;	100%

methanol (67-56-1) + 2-fluoro-4-nitrobenzoic acid (403-24-7) → 2-fluoro-4-nitro-benzoic acid methyl ester (392-09-6)

Conditions	Yield
With sulfuric acid for 4h; Reflux;	99%
With sulfuric acid Reflux;	98%
With sulfuric acid for 15h; Reflux; Large scale;	95%

2-fluoro-4-nitrobenzoic acid (403-24-7) + methylamine (74-89-5) → 2-(methylamino)-4-nitro-benzoic acid (49565-62-0)

Conditions	Yield
In ethanol at 80℃; for 16h; Sealed tube;	91%

2-fluoro-4-nitrobenzoic acid (403-24-7) + ethyl 5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxylate hydrobromide → ethyl 6-(2-fluoro-4-nitrobenzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxylate

Conditions	Yield
Stage #1: 2-fluoro-4-nitrobenzoic acid With thionyl chloride In dichloromethane for 2h; Reflux; Stage #2: ethyl 5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxylate hydrobromide With pyridine In acetonitrile at 20 - 50℃; for 5h;	88%

2-fluoro-4-nitrobenzoic acid (403-24-7) → 2-fluoro-4-nitrobenzamide (350-32-3)

Conditions	Yield
Stage #1: 2-fluoro-4-nitrobenzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 25℃; for 4h; Stage #2: With ammonia In water for 0.166667h;	85%
With pyridine; ammonium chloride; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In ethyl acetate	53%
With pyridine; ammonium chloride; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide	53%

2-fluoro-4-nitrobenzoic acid (403-24-7) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → 2-fluoro-N-methoxy-N-methyl-4-nitrobenzamide (774239-17-7)

Conditions	Yield
With pyridine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 60℃; for 15h;	85%
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃;

2-fluoro-4-nitrobenzoic acid (403-24-7) → 4-nitro-2-fluorobenzaldehyde (157701-72-9)

Conditions	Yield
With borane-THF In tetrahydrofuran at 80℃; for 3h;	83%

2-fluoro-4-nitrobenzoic acid (403-24-7) + N,N-dimethylammonium chloride (506-59-2) → 2-fluoro-N,N-dimethyl-4-nitro-benzamide (1187368-66-6)

Conditions	Yield
With ethylene dichloride hydrochloride; benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 12h;	81%
Stage #1: 2-fluoro-4-nitrobenzoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 1h; Stage #2: N,N-dimethylammonium chloride With triethylamine In dichloromethane for 1h;	60%

1-methyl-4-aminopiperidine (41838-46-4) + 2-fluoro-4-nitrobenzoic acid (403-24-7) → 2-fluoro-N-(1-methyl-4-piperidyl)-4-nitro-benzamide (957855-56-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In ISOPROPYLAMIDE at 20℃; for 4h;	78%
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 18 - 25℃; for 18h;	59%
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 17 - 25℃; for 18h;	59%
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 18 - 25℃; for 18h;	59%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20 - 40℃;

2-fluoro-4-nitrobenzoic acid (403-24-7) → 2-fluoro-4-nitro-1-(trifluoromethyl)benzene (69411-67-2)

Conditions	Yield
With sulfur tetrafluoride; hydrogen fluoride at 85℃; for 24h; Autoclave; Inert atmosphere;	78%

2-fluoro-4-nitrobenzoic acid (403-24-7) + tert-butyl alcohol (75-65-0) → tert-butyl 2-fluoro-4-nitrobenzoate (157665-46-8)

Conditions	Yield
With pyridine; p-toluenesulfonyl chloride at 0℃; for 19h;	75%
With pyridine; p-toluenesulfonyl chloride at 0℃; for 19h;	75%
With pyridine; p-toluenesulfonyl chloride 1.) 15 deg C, 5 min, 2.) RT, 2.5 h; Yield given. Multistep reaction;
With pyridine; p-toluenesulfonyl chloride for 19h;	524 mg

t-butoxycarbonylhydrazine (870-46-2) + 2-fluoro-4-nitrobenzoic acid (403-24-7) → N'-(2-fluoro-4-nitrobenzoyl)hydrazinecarboxylic acid tert-butyl ester (590421-50-4)

Conditions	Yield
With 3-methyl-N-(3-methylbutyl)-1-butanamine; HATU In N,N-dimethyl-formamide at 20℃;	57%
Stage #1: 2-fluoro-4-nitrobenzoic acid With N-ethyl-N,N-diisopropylamine; HATU In DMF (N,N-dimethyl-formamide) at 20℃; for 0.333333h; Stage #2: t-butoxycarbonylhydrazine In DMF (N,N-dimethyl-formamide) at 20℃;	57%

2-fluoro-4-nitrobenzoic acid (403-24-7) + phenylmethanethiol (100-53-8) → 2-(benzylsulfanyl)-4-nitrobenzoic acid (92163-95-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 65℃; for 35h;	55.5%

(14S,16S,32R,33R,2R,4S,10E,12E,14R)-86-chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl methyl-L-alaninate (77668-69-0) + 2-fluoro-4-nitrobenzoic acid (403-24-7) → C39H46ClFN4O12

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 72h; Inert atmosphere;	35%

Upstream product

• 1427-07-2 2-fluoro-4-nitrotoluene 
• 866579-96-6 1-(2-fluoro-4-nitrophenyl)ethanone 
• 64-19-7 acetic acid 

Downstream Products

• 446-31-1 2-fluoro-4-aminobenzoic acid 
• 403-23-6 2-fluoro-4-nitrobenzoyl chloride 
• 392-09-6 2-fluoro-4-nitro-benzoic acid methyl ester 
• 393-95-3 2-fluoro-4,5-dinitro-benzoic acid 
• 157665-46-8 tert-butyl 2-fluoro-4-nitrobenzoate 
• 350-32-3 2-fluoro-4-nitrobenzamide 
• 957855-56-0 2-fluoro-N-(1-methyl-4-piperidyl)-4-nitro-benzamide 
• 774239-17-7 2-fluoro-N-methoxy-N-methyl-4-nitrobenzamide 
• 73792-08-2 methyl 4-amino-2-fluorobenzoate 
• 232950-90-2 5-(S)-Acetamidomethyl-3-[4'-formyl-3'-fluorophenyl]oxazolidine-2-one 
• 840501-15-7 (4-amino-2-fluorophenyl)methanol 
• 840501-16-8 (3-fluoro-4-hydroxymethyl-phenyl)-carbamic acid benzyl ester 
• 840501-17-9 [4-(tert-butyl-dimethyl-silanyloxymethyl)-3-fluoro-phenyl]-carbamic acid benzyl ester 
• 1026347-56-7 2-fluoro-4-mercaptobenzoic acid 

Relevant academic research and scientific papers

RETINOID COMPOUND AND PHARMACEUTICAL COMPOSITION

PROBLEM TO BE SOLVED: To provide a novel retinoid compound that is low in teratogenicity, and a pharmaceutical composition containing said retinoid compound. SOLUTION: Provided are a retinoid compound which is a compound represented by the following formula (1) or a salt thereof, and a pharmaceutical composition containing said retinoid compound. In the formula, R1 represents a halogen atom, and R2 and R3 each independently represent a silyl group. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT

Continuous synthesis method for substituted benzoic acid organic matter

The invention provides a continuous synthesis method for a substituted benzoic acid organic matter. The continuous synthesis method comprises the following steps: in the presence of a catalyst and anorganic solvent, continuously putting an organic matter of a formula (I) shown in the specification, and oxygen into a continuous reaction device, carrying out a continuous oxidation reaction so as toobtain the substituted benzoic acid organic matter, and continuously discharging the substituted benzoic acid organic matter, wherein the substituted benzoic acid organic matter is of a structure ofa formula (II) shown in the specification. Oxygen is a green reagent and is cheap and easy to obtain, a great amount of wastes are not generated after reactions are completed, and the system is easy to treat. Due to continuous reaction operation, the risk that the solvent has flash evaporation explosion because of high-concentration oxygen in in-batch reactions can be reduced. Under same oxidationconditions, due to a continuous preparation process, escape of oxygen can be reduced, the utilization rate of oxygen can be greatly increased, operation can be also simplified, the security of reactions can be improved, and the yield of the substituted benzoic acid organic matter can be increased.

Prostatic cancer treatment medicine

The invention relates to a compound with a prostatic cancer treatment function and nontoxic pharmaceutically acceptable salt of the compound. The structure of the compound is as shown in a formula I,wherein X is C or N, R1 is alkyl of C1-C3 or halogen substituted alkyl, R2 is alkyl of C1-C3 and halogen substituted alkyl or halogen, R3 and R4 are independently selected from H, alkyl and substituted alkyl, and R3 and R4 are connected to form cycloalkyl. The compound has high inhibiting effects on in-situ prostate cancer and transfer of the prostate cancer, and eclamptogenic side effects are lower.

Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents

Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.

PROCESS FOR THE PREPARATION OF ENZALUTAMIDE

The present invention provides a process for the preparation of enzalutamide.

Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)

A structure-activity relationship study was carried out on a series of thiohydantoins and their analogues 14 which led to the discovery of 92 (MDV3100) as the clinical candidate for the treatment of hormone refractory prostate cancer.

1(2)H-tetrazol-5-yl-phenyl-oxazolidinones as antibacterial agents

The present invention provides a class of phenyl-oxazolidinones of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is a radical of formula (i) or formula (ii): methods of preparing such compounds, pharmaceutical compositions comprising one or more of such compounds, and the use thereof in the manufacture of a medicament which is used in the treatment of bacterial infections.

NOVEL OXAZOLIDINONE COMPOUNDS AS ANTIINFECTIVE AGENTS

The present invention relates to novel oxazolidinone compounds of formula (I) with antibacterial activity, their pharmaceutically acceptable salts, their stereoisomers, their prodrugs, pharmaceutical compositions comprising the same and to their use as therapeutic agents

Diarylthiohydantoin compounds

The present invention relates to diarylthiohydantoin compounds and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer.

DIARYLHYDANTOIN COMPOUNDS

The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for syntheszing them and using them in the treatment of hormone refractory prostate cancer.