30459-70-2

Usage

Uses

Used in Pharmaceutical Synthesis:
2-Methyl-4-nitrobenzoyl chloride is used as an intermediate in the synthesis of 7-Chloro-1,2,3,4-tetrahydro-1-(2-methyl-4-nitrobenzoyl)-5H-1-benzazepin-5-one (C366123), which is a key compound in the production of Tolvaptan-d7 (T536652). Tolvaptan-d7 is a labelled version of Tolvaptan (T536650), a selective, competitive arginine vasopressin V2 receptor antagonist.
Used in the Treatment of Hyponatraemia:
2-Methyl-4-nitrobenzoyl chloride, through its role in the synthesis of Tolvaptan, is indirectly used for the treatment of hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan, as a V2 receptor antagonist, helps regulate water balance in the body and increase the excretion of water by the kidneys, thereby addressing the underlying cause of hyponatremia.

Synthetic route

2-methyl-4-nitrobenzoic acid (1975-51-5) → 2-methyl-4-nitrobenzoyl chloride (30459-70-2)

Conditions	Yield
With thionyl chloride
With thionyl chloride Heating;
With thionyl chloride Substitution;

methanol (67-56-1) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → methyl 2-methyl-4-nitrobenzoate (62621-09-4)

Conditions	Yield
In dichloromethane at 0℃; for 0.5h;	100%
In dichloromethane at 0℃; for 0.5h;	100%

2,2-dimethylpropionic acid 7-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl ester (863762-10-1) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → 2,2-dimethylpropionic acid 7-chloro-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl ester (863762-20-3)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h;	98%
With triethylamine In dichloromethane at 0 - 20℃; for 1.25h;	98%

2,2-dimethylpropionic acid 7-fluoro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl ester (863762-12-3) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → 2,2-dimethylpropionic acid 7-fluoro-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl ester (863762-22-5)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h;	97%

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-nitro-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137982-91-3)

Conditions	Yield
Stage #1: 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one With magnesium hydroxide In acetonitrile at 10℃; for 0.5h; Stage #2: 2-methyl-4-nitrobenzoyl chloride In acetonitrile for 5h;	95%
With sodium hydroxide In acetonitrile at 20℃; for 1h;	73%
With triethylamine In dichloromethane at 20℃; for 2h; Acylation;	32%

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + 7-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepine (313673-94-8) → (7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)-2-methyl-4-nitrobenzamide (313673-96-0)

Conditions	Yield
With pyridine In dichloromethane for 1h;	91%

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + C13H16ClNO4 → C21H21ClN2O7

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Reagent/catalyst;	88.7%

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + ethyl 4-(4-chlorophenylamino)butanoate → C20H21ClN2O5

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 3h; Reagent/catalyst;	88%

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + methyl 4-(2-amino-5-chlorophenyl)-4-oxobutyrate (80452-54-6) → C19H17ClN2O6 (1417520-49-0)

Conditions	Yield
With pyridine In dichloromethane	87%

L-glutamic acid diethyl ester (16450-41-2) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → diethyl N-(2-methyl-4-nitrobenzoyl)-L-glutamate (80015-10-7)

Conditions	Yield
With pyridine In toluene at 0 - 25℃; for 1.5h;	77%

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + 4-methoxy-aniline (104-94-9) → N-(4-Methoxy-phenyl)-2-methyl-4-nitro-benzamide (101971-73-7)

Conditions	Yield
In pyridine Heating;	75%

L-glutamic acid (56-86-0) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → N-(2-methyl-4-nitro-benzoyl)-L-glutamic acid

Conditions	Yield
With sodium hydroxide

1-tert-butylamino-2,3-dihydroxypropane (22741-52-2) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → 2-Methyl-4-nitro-benzoic acid 3-tert-butylamino-2-hydroxy-propyl ester (90531-58-1)

Conditions	Yield
With pyridine In toluene for 2h; Ambient temperature;

diazomethane (186581-53-3, 908094-01-9) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → 2-Diazo-1-(2-methyl-4-nitro-phenyl)-ethanone (50712-65-7)

Conditions	Yield
In diethyl ether

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + 10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine (22162-53-4) → (5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)-(2-methyl-4-nitro-phenyl)-methanone (1027943-31-2)

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + 3,4,5,10,11,11a-hexahydro-1H-2-thia-4a,10-diazadibenzo[a,d]cycloheptene (705966-36-5) → (2-methyl-4-nitro-phenyl)-(3,4,11,11a-tetrahydro-1H,5H-2-thia-4a,10-diaza-dibenzo[a,d]cyclohepten-10-yl)-methanone

Conditions	Yield
With triethylamine In dichloromethane

1H-pyrrolo[2,3-b]pyridin-5-amine (100960-07-4) + 2-methyl-4-nitrobenzoyl chloride (30459-70-2) → 2-methyl-5-nitro-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)-benzamide (1012342-27-6)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 16h;

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → (4-amino-2-methyl-phenyl)-(3,4,11,11a-tetrahydro-1H,5H-2-thia-4a,10-diaza-dibenzo[a,d]cyclohepten-10-yl)-methanone

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 2: Zn; NH4Cl / methanol View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → biphenyl-2-carboxylic acid [3-methyl-4-(3,4,11,11a-tetrahydro-1H,5H-2-thia-4a,10-diaza-dibenzo[a,d]cycloheptene-10-carbonyl)-phenyl]-amide

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / CH2Cl2 2: Zn; NH4Cl / methanol 3: Et3N / CH2Cl2 View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → (4-amino-2-methyl-phenyl)-(7-chloro-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl)-methanone

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / pyridine / CH2Cl2 / 1 h 2: 97 percent / SnCl2*2H2O / ethanol / 3 h / Heating View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → tolvaptan (150683-30-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 32 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 39 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C 3: 53 percent / Et3N / CH2Cl2 / 1.5 h / 20 °C 4: 30 percent / NaBH4 / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate / dichloromethane; water / pH 7 - 8 2.1: tin(ll) chloride / methanol / 16 h / 20 °C 3.1: sodium hydrogencarbonate / dichloromethane / 0 - 5 °C / pH 7 - 8 4.1: sodium tetrahydroborate; methanol / 1 h / 20 °C 4.2: pH 6 - 7 View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 2.1: tin(IV) chloride / methanol / 16 h / 20 °C 3.1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 4.1: sodium tetrahydroborate / methanol / 1 h / 20 °C 4.2: pH 6.0 - 7.0 View Scheme
Multi-step reaction with 4 steps 1.1: magnesium hydroxide / acetonitrile / 0.5 h / 10 °C 1.2: 5 h 2.1: methanol; tin(II) chloride dihdyrate / 23 h / 10 °C 3.1: magnesium hydroxide / dichloromethane; water / 0.5 h / 10 °C 3.2: 3 h 4.1: sodium tetrahydroborate; methanol / 1 h View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137977-97-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 32 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 39 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / dichloromethane; water / pH 7 - 8 2: tin(ll) chloride / methanol / 16 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 2: tin(IV) chloride / methanol / 16 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: magnesium hydroxide / acetonitrile / 0.5 h / 10 °C 1.2: 5 h 2.1: methanol; tin(II) chloride dihdyrate / 23 h / 10 °C View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → MOP-21826 (137973-76-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 32 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 39 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C 3: 53 percent / Et3N / CH2Cl2 / 1.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / dichloromethane; water / pH 7 - 8 2: tin(ll) chloride / methanol / 16 h / 20 °C 3: sodium hydrogencarbonate / dichloromethane / 0 - 5 °C / pH 7 - 8 View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 2: tin(IV) chloride / methanol / 16 h / 20 °C 3: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 View Scheme
Multi-step reaction with 3 steps 1.1: magnesium hydroxide / acetonitrile / 0.5 h / 10 °C 1.2: 5 h 2.1: methanol; tin(II) chloride dihdyrate / 23 h / 10 °C 3.1: magnesium hydroxide / dichloromethane; water / 0.5 h / 10 °C 3.2: 3 h View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → (4-Amino-2-methyl-phenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)-methanone (211099-25-1)

Conditions	Yield
Multi-step reaction with 2 steps 2: H2 / Pd/C View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → N-[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)-3-methyl phenyl]-5-fluoro-2-methylbenzamide

Conditions	Yield
Multi-step reaction with 3 steps 2: H2 / Pd/C View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → diethyl N-(4-amino-2-methylbenzoyl)-L-glutamate (80014-85-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77 percent / pyridine / toluene / 1.5 h / 0 - 25 °C 2: 81 percent / H2 / 10percent Pd/C / ethanol / 760 Torr View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → diethyl N-<2-methyl-4-(prop-2-ynylamino)benzoyl>-L-glutamate (80014-86-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 77 percent / pyridine / toluene / 1.5 h / 0 - 25 °C 2: 81 percent / H2 / 10percent Pd/C / ethanol / 760 Torr 3: 37 percent / 2,6-lutidine / N,N-dimethyl-acetamide / 48 h / Ambient temperature View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → N-<2-methyl-4-prop-2-ynylamino>benzoyl>-L-glutamic acid (80014-99-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 77 percent / pyridine / toluene / 1.5 h / 0 - 25 °C 2: 81 percent / H2 / 10percent Pd/C / ethanol / 760 Torr 3: 37 percent / 2,6-lutidine / N,N-dimethyl-acetamide / 48 h / Ambient temperature 4: 39 percent / CaCO3 / N,N-dimethyl-acetamide / 48 h / Ambient temperature 5: 38 percent / aq. NaOH / ethanol / 18 h / Ambient temperature View Scheme

2-methyl-4-nitrobenzoyl chloride (30459-70-2) → diethyl N-<2-methyl-4-prop-2-ynylamino>benzoyl>-L-glutamate (80014-80-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 77 percent / pyridine / toluene / 1.5 h / 0 - 25 °C 2: 81 percent / H2 / 10percent Pd/C / ethanol / 760 Torr 3: 37 percent / 2,6-lutidine / N,N-dimethyl-acetamide / 48 h / Ambient temperature 4: 39 percent / CaCO3 / N,N-dimethyl-acetamide / 48 h / Ambient temperature View Scheme

Upstream product

• 1975-51-5 2-methyl-4-nitrobenzoic acid 

Downstream Products

• 80015-10-7 diethyl N-(2-methyl-4-nitrobenzoyl)-L-glutamate 
• 90531-58-1 2-Methyl-4-nitro-benzoic acid 3-tert-butylamino-2-hydroxy-propyl ester 
• 101971-73-7 N-(4-Methoxy-phenyl)-2-methyl-4-nitro-benzamide 
• 1027943-31-2 (5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)-(2-methyl-4-nitro-phenyl)-methanone 
• 137982-91-3 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 150683-30-0 tolvaptan 
• 137977-97-0 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 137973-76-3 MOP-21826 
• 50712-66-8 (2-Methyl-4-nitro-phenyl)-acetic acid ethyl ester 
• 50712-55-5 ethyl 2-(4-amino-2-methylphenyl)acetate 
• 62621-10-7 2-methyl-4-nitro-benzoic acid ethyl ester 
• 80014-85-3 diethyl N-(4-amino-2-methylbenzoyl)-L-glutamate 
• 305360-97-8 C₁₁H₉N₃O₃S 
• 851202-63-6 4-amino-2-methyl-N-thiazol-2-ylbenzamide 

Relevant academic research and scientific papers

Intramolecular electron transfer reactions in meso-(4-nitrophenyl)-substituted subporphyrins

A2B-type meso-(4-nitrophenyl)-substituted subporphyrins have been synthesized and shown to undergo very fast photoinduced intramolecular charge separation (CS) and charge recombination (CR) between the subporphyrin core and the meso-4-nitrophenyl group in CH2Cl2 as probed by femtosecond time-resolved transient absorption spectroscopy. Red-shifted emissions were detected from charge-separated states as a rare case for porphyrinoids.

Augmenting the Activity of Macrolide Adjuvants against Acinetobacter baumannii

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Spiro-bis-benzoxazole diamine and preparation method and application thereof, polyimide and preparation method and application thereof

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HETEROCYCLIC COMPOUNDS AS AHR MODULATORS

The present invention relates compounds of the general formula (I) or (III) which are ARH inhibitors, methods for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds and pharmaceutical compositions for the treatment or prevention of diseases, in particular cancer or conditions with dysregulated immune functions, or other conditions associated with aberrant AHR signalling, as a sole agent of in combination with other active ingredients. Such compounds may also be of utility in the expansion of hematopoietic stem cells (HSCs) and the use of HSCs in autologous or allogenic transplantation for the treatment of patients with inherited immunological and autoimmune diseases and diverse hematopoietic disorders.

A method of preparing intermediates the request cuts down the Pu Tanzania

The invention relates to a method for preparing a tolvaptan intermediate, namely 7-chlorine-5-oxo-1-(2-methyl-4-nitrobenzene formyl)-1,2,3,4-tetrahydro-benzo-azepine. The tolvaptan intermediate which is a compound as shown in the formula (1) is obtained by 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo-azepine (2) reacting with 4-nitryl-2-methylbenzene formyl chloride (3). The tolvaptan intermediate prepared by the method has the advantages of high purity, high yield and short reaction time, thereby being suitable for large-scale industrialized production.

MACROCYCLIC FACTOR VIIA INHIBITORS

The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.

MACROCYCLIC FACTOR VIIA INHIBITORS

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.

Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)- 3,5-difluorobenzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A phosphonooxymethylene prodrug of a potent and selective hA2A receptor antagonist

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BETA- AND GAMMA-AMINO-ISOQUINOLINE AMIDE COMPOUNDS AND SUBSTITUTED BENZAMIDE COMPOUNDS

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