Category: 60091-87-4

Mayer, W. published the artcileThe pharmaceutical characterization and spectroscopy of AWD 26-06, Recommanded Product: 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, the publication is Pharmazie (1990), 45(8), 565-7, database is CAplus and MEDLINE.

Data are given on the TLC, stability, assay, and spectroscopic characteristics of the antiulcer drug AWD 26-06 (I). Brief TLC data are also given on 4 other compounds formed during the synthesis (not reported here) of I.

Pharmazie published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C13H9ClN2O4, Recommanded Product: 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Venkat Rao, S. published the artcileA Cu (I) catalyzed large scale synthesis of an antipsychotic drug substance Clozapine with new precursor 2-chloro benzoic acid, Category: chlorides-buliding-blocks, the publication is Arabian Journal of Chemistry (2020), 13(7), 6040-6043, database is CAplus.

Development of an economic and com. manufacturing process for an anti-psychotic drug substance clozapine I with an alternative key starting material (2-chloro benzoic acid) in the place of literature reported key starting material Anthranilic acid. To avoid narcotic key starting materials usage in drug substances the author invented a com. available raw material 2-chlorobenzoic acid, which reacts with another key starting material 4-chloro-1,2-diamino benzene. This reaction proceeded through Ullman reaction to produce multi scale level Clozapine which quality meets the ICH requirements.

Arabian Journal of Chemistry published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C10H12BNO3S, Category: chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Yu, Yongguo published the artcileDesign, synthesis and anticancer activity evaluation of diazepinomicin derivatives, Category: chlorides-buliding-blocks, the publication is Letters in Drug Design & Discovery (2013), 10(4), 369-373, 5 pp., database is CAplus.

A series of diazepinomicin derivatives [5,10-dihydro-4,6,8-trihydroxy-10-[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrien-1-yl]-11H-dibenzo[b,e][1,4]diazepin-11-one derivatives] were synthesized and evaluated in vitro for their growth inhibitory activity against the human carcinoma cell lines. The results indicated the anticancer selectivity of this kind of compounds Based on the results, preliminary structure-activity relationships were discussed. The synthesis of the target compounds was achieved using 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one derivatives and (2E,6E)-1-bromo-3,7,11-trimethyl-2,6,10-dodecatriene (trans,trans-farnesyl bromide) as key intermediates. The title compounds thus formed included a diazepinomicin analog (I) and related substances.

Letters in Drug Design & Discovery published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C5H5ClIN, Category: chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Wrobel, Zbigniew published the artcileThe reported formation of 5H-dibenzo [b,e][1,4]diazepin-11( 10H )-ones in the noncatalyzed, base-promoted double arylation of anthranilamide revisited. Correction of some product structures, Category: chlorides-buliding-blocks, the publication is Journal of Heterocyclic Chemistry (2021), 58(9), 1802-1808, database is CAplus.

The base-promoted reaction of 2-halonitro- or 1,2-dihalobenzenes with anthranilamide reported by Cao, Ma et al. (Synthesis2013, 45, 111) was reinvestigated. Some of the products reported, which was identified as dibenzodiazepinones, were actually benzoxazole derivatives In this paper, the correct structures of these products were established and confirmed by independent synthesis. For four other products, the supposed structures were found to be incompatible with the dibenzodiazepinones that were synthesized by the reliable method used.

Journal of Heterocyclic Chemistry published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C6H17NO3Si, Category: chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Neyt, N. C. published the artcileBatch-flow hybrid synthesis of the antipsychotic clozapine, Name: 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, the publication is Reaction Chemistry & Engineering (2018), 3(1), 17-24, database is CAplus.

The implementation of an on-the-fly purification by trituration which was also utilized to perform solvent swaps. This above concept demonstrated through the synthesis of the antipsychotic clozapine. In addition, reported a novel means of performing a reduction of an aryl nitro group under flow conditions and an overall improved process route for the total synthesis of clozapine.

Reaction Chemistry & Engineering published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C13H9ClN2O4, Name: 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Rueger, Carla published the artcileNew derivatives of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-ones with anticholinergic activity, Safety of 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, the publication is Pharmazie (1990), 45(8), 555-9, database is CAplus.

Condensation of 4,2-R(O₂N)C₆H₃Cl (R = H, Cl) with 2-H₂NC₆H₄CO₂H gave 2-[4,2-R(O₂N)C₆H₃NH]C₆H₄CO₂H (same R). The reduction of the latter gave 2-[4,2-R(H₂N)C₆H₃NH]C₆H₄CO₂H which upon cyclocondensation gave 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one and its 8-chloro derivative The latter products were acylated or methylated and acylated to give 5-acyl-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-ones I (R = H, Cl; R¹ = H, Me; R² = Cl, CH₂Cl, etc.); the I thus obtained were aminated to give I [R = H, Cl; R¹ = H, Me; R² = N(CH₂CH₂OH)₂, NMe(CH₂CH₂OH), etc.] (II). The ulcer-inhibiting activity of II was postulated; II (R = Cl; R¹ = H; R² = N(CH₂CH₂)H)].HCl, i.e. AWD 26-06, is selected for clin. evaluation (no data). II thus prepared differ from other tricyclic psychopharmaceuticals in their lipid solubility and hence have no effect as central nervous system agents.

Pharmazie published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C13H9ClN2O4, Safety of 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Wang, Fuxiang published the artcileSynthesis of clozapine, Related Products of chlorides-buliding-blocks, the publication is Zhongguo Yiyao Gongye Zazhi (2013), 44(10), 969-971, database is CAplus.

Compounds 2,5-dichloronitrobenzene and anthranilic acid were reacted in the presence of potassium carbonate with DMF as solvent to produce 2-(4-chloro-2-nitroanilino)benzoic acid, which was reduced to 2-(2-amino-4-chloroanilino)benzoic acid (5) by hydrazine hydrate and FeCl₃· 6H₂O. Catalyzed by polyphosphoric acid in xylene, compound 5 was cyclized into 8-chloro-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one, which was coupled with N-methylpiperazine in the presence of titanium tetrachloride to give clozapine. The overall yield was 43%, based on 2,5-dichloronitrobenzene.

Zhongguo Yiyao Gongye Zazhi published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C24H20Ge, Related Products of chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Hunziker, F. published the artcileChemistry and pharmacology of dibenzo[b,e][1,4]diazepine derivatives with basic substituents in position 10, Quality Control of 60091-87-4, the publication is Arzneimittel-Forschung (1963), 324-8, database is CAplus and MEDLINE.

A series of I derivatives was prepared according to Clemo, et al. (CA 19, 293) and Burton and Gibson (CA 19, 987) by an Ullmann-synthesis from o-bromonitrobenzenes and free anthranilic acid derivatives in presence of K₂CO₃ and catalytic amounts of Cu in a higher alcohol as solvent. The N-methylated anthranilic acids gave lower yields (50-60%) than the corresponding primary amines. The esters of I were best obtained via the acid chlorides. Thus, the following I derivatives were prepared (R¹, R², R³, and m.p. given): H, 4-Me, H, 213-15°; H, 4-Me, Et, 99-100°; Me, 4-Me, H, 140-1°; H, 4-Cl, H, 245-8°; H, 4-Cl, Et, 134-6°; Me, 4-Cl, H, 139-42°; H, 4-CF₃, H, 225-6°; H, 4-CF₃, Me, 147-8°; Me, 4-CF₃, H, 154-6°; H, 4-OMe, H, 228-30°; H, OMe, Et, 104°; Me, 4-OMe, H, 164-6°; H, 5-Cl, Me, 157-8°; H, 5-Cl, Et, 127-8°; Me, 5-Cl, H, 160°; Me, 5-Cl, Me, 92-3°; H, 5-OMe, Me, 149°; H, 5-SMe, Et, 187-8°; Me, 5-SMe, Me, 102-3°; H, 6-Cl, Me, 119-20°; H, 5′-Cl, Et, 106-7°; H, 5′-OMe, H, 235-7°; H, 4′-Cl, H, 232-5°; H, 4′-Cl, Me, 138°; H, 4′-OMe, H, 240°; Me, 4′-OMe, H, 168-72°. To a cooled solution of 5.9 g. K in 110 ml. tert-BuOH was added under stirring 12 g. MeSH. At 20°, a solution of 40.3 g. I (R¹ = R³ = Me, R² = 5-Cl) in 300 ml. HCONMe₂ was added. After 2 hrs. stirring at 80°, evaporation to dryness in vacuo, distribution between benzene and NaHCO₃ solution, evaporation of the benzene, and crystallization from Et₂O/petr. ether gave 40 g. I (R¹ = R³ = Me, R² = 5-SMe), m. 102-3°. To 135.6 g. I (R¹ = R³ = H, R² = 5-Cl) 10.3, suspended in 1.8 l. 2N aqueous NH₃ was added within 3 hrs. 266 g. Na₂S₂O₄. The mixture was heated to 80° till solution was complete. Charcoal treatment, acidification to pH 4.5 with AcOH, addition of NaCl, and work-up gave 121.3 g. II (R¹ = R³ = H, R² = 5-Cl), m. 208-5° (decomposition) (MeOH-H₂O). Similarly prepared were the II derivatives (R¹, R², R³, m.p. given): H, 4-Me, H, 213-15°; Me, 4-Me, H, 144-6°; H, 4-Cl, H, 200-5°; Me, 4-Cl, H, 155°; H, 4-CF₃, H, 214-15°; Me, 4-CF₃, H, 160°; H, 4-OMe, H, 200°; Me, 4-OMe, H, 132-4°; H, 5-Cl, Me, 117-18°; Me, 5-Cl, H, 155°; H, 5-OMe, H, 178-9°; H, 5-SMe, H, 170-2°; H, 6-Cl, Me, 135-9°; H, 5′-Cl, H, 175-7°; H, 5′-OMe, H, 182-4°; H, 4′-Cl, H, 197-8°. II (R¹ = R³ = H, R² = 5-Cl) (121.3 g.) was refluxed in 3 l. xylene 40 hrs. under continuous removal of H₂O. After distillation of the solvent and vapor distillation for removal of impurities, the residue was made alkaline with dilute NH₃, filtered, treated with charcoal, and crystallized from Me₂CO-H₂O to give 71.3 g. III (R¹ = H, R² = 7-Cl), m. 253-4°. The same compound was also obtained by refluxing of 2.5 g. II (R¹ = H, R² = 5-Cl, R³ = Me) with 0.39 g. NaNH₂ in 20 ml. dioxane, dilution with H₂O, and filtration in 83% yield. Similarly prepared were the following III derivatives (R¹, R², m.p. given): H, 2-Cl, 259-60°; H, 2-OMe, 220-1°; Me, 2-OMe, 200-12°; H, 3-Cl, 271°; H, 3-OMe, 232-3°; H, 3-Me, 267-9°; H, 6-Cl, 244-6°; Me, 7-Cl, 226-7°; H, 7-OMe, 239-40°; H, 7-SMe, 211-12°; Me, 7-SMe, 225-6°; H, 8-Cl, 231-2°; Me, 8-Cl, 214-15°; H, 8-Me, 194-5°; Me, 8-Me, 228-9°; H, 8-CF₃, 176-7°; Me, 8-CF₃, 239-40°; H, 8-OMe, 174-6°; Me, 8-OMe, 221-3°. III (R¹ = H, R² = 7-Cl) (52.5 g.) was refluxed 1 hr. with 9.2 g. NaNH₂ in 350 ml. dioxane, then 29 g. ClCH₂CH₂NMe₂ in 50 ml. benzene was added and the mixture refluxed 16 hrs. Concentration in vacuo, distribution between benzene/H₂O, extraction of the benzene with diluted HCl, alkalinization of the extract with NH₃, extraction with CHCl₃, evaporation of the solvent, and crystallization from Me₂CO/Et₂O gave 50.8 g. IV (R¹ = H, R² = 7-Cl), m. 165-6°, _ε230 32,740 (EtOH); hydrochloride m. 225-33° (EtOH-Et₂O). The same compound was obtained by refluxing 11.4 g. II (R¹ = H, R² = 5-Cl, R³ = Me) 90 min. with 1.8 g. NaNH₂ in 90 ml. dioxane, then adding 6 g. ClCH₂CH₂NMe₂ in 20 ml. benzene, and refluxing 15 hrs. (and usual work-up) in 56% yield. Similarly prepared were the following IV derivatives (R¹ R², m.p. free base, m.p. hydrochloride, L.D.₅₉ mg./kg. mouse per os given): H, H, 112-14°, -, 705; Me, H, 116-17°, 234-40°, 215; H, 2-Cl, 172-3°, -, 175; Me, 2-OMe, -, 205-10°, 900; H, 3-Cl, 159-60°, -, 305; H, 3-OMe, 141-3°, -, 150; H, 6-Cl, 122-3°, -, 260; H, 7-Cl, 165-6°, 225-33°, 330; Me, 7-Cl, -, 247-53°, 500; H, 7-OMe, 152-3°, -, 220; H, 7-SMe, 126-9°, -, 345; Me, 7-SMe, -, 205-7°, 520; H, 8-Cl, 140-5°, -, -; Me, 8-Cl, -, 240-5°, 500; H, 8-OMe, 126-7°, -, 220; H, 8-CF₃, 115-18°, -, 150; Me, 8-CF₈, -, 222-6°, 240; H, 8-Me, 137-8°, -, 127; Me, 8-Me, -, 214-17°, 100. Also prepared were the V derivatives (X, m.p., D.L.₅₀ mg./kg. mouse per os given): 2-pyrrolidinoethyl, 159-60°, 700; 2-piperidinoethyl, 187-9°, 700; 2-morpholinoethyl, 220-2°, >2500; CH₂CHMeNMe₂, 197-9°, 320; (CH₂)₃NMe₂, 137-9°, 1000. Reduction of the corresponding oxo derivatives with LiAlH₄ in tetrahydrofuran gave the VI derivatives (R¹, R², m.p., L.D.₅₀ mg./kg. mouse per os given): H, H, (maleate m. 100°), 600; Me, H, – (maleate m. 149-51°), 760; H, Cl, 87-9°, 275. IV (R¹ = H, R² = 2-Cl) (20 g.) was refluxed 24 hrs. in 200 ml. 5N HCl. Concentration in vacuo, addition of NaOH, and isolation of the resulting base gave 14.8 g. VII, b_8.97 130-8°. Acetylation with Ac₂O in pyridine gave VIII, m. 109-11°. To prove the structure, VIII was also synthesized independently. Thus, IX was acetylated to give X, m. 89-90° (Et₂O-petr. ether). X (31 g.) was alkylated with 4 g. NaNH₂ and 9.5 g. ClCH₂CH₂NMe₂ in 150 ml. dioxane to give after usual work-up 31.5 g. VIII. To test the influence of the N bridge on the pharmacol. properties, XI was prepared by refluxing 11.7 g. phenanthridone with 2.95 g. NaNH₂ in 120 ml. dioxane for 2 hrs. Addition of 7 g. ClCH₂CH₂NMe₂ in 50 ml. dioxane during 4 hrs., refluxing for 10 hrs, and normal work-up gave XI; hydrochloride m. 268-70° (MeOH-Et₂O). The XII derivatives were also prepared (X, m.p., L.D.₅₀ mg./kg. mouse per os given): S, 268-71° (hydrochloride) 870; SO₂, 113-23°, 620; O, 230-3° (hydrochloride), 500. The influence of the chem. constitution on the pharmacological activity was studied. A heterocyclic bridge in position 5 is indispensable for activity; derivatives of benzanilide and phenanthridone having basic substituents are inactive. An unsubstituted NH-group in position 5 has a more favorable effect than the Me-substituted N and is superior in activity to other hetero-bridges such as SO₂, S, and O. Compounds with substituents in position 7 show greater activity than the unsubstituted compound A carbonyl group in position 11 is essential for activity, the corresponding VI derivatives, although closely related to known antihistamines of the benzylaniline group are practically inactive in vivo. In agreement with other classes of antihistamines, the (CH₂)₂NMe₂ and (CH₂)₃NMe₂ groups are the most effective basic substituents. IV (R¹ = H, R² = 7-Cl) and the corresponding 7-SMe derivative belong to the most potent antihistaminics of today.

Arzneimittel-Forschung published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C13H9ClN2O4, Quality Control of 60091-87-4.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Watanabe, Hitoshi published the artcileSynthesis and pharmacological evaluation of 11-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepines with clozapine-like receptor occupancy at dopamine D₁/D₂ receptor, Category: chlorides-buliding-blocks, the publication is Bioorganic & Medicinal Chemistry Letters (2020), 30(21), 127563, database is CAplus and MEDLINE.

Clozapine-like compound without agranulocytosis risk is need to cure the treatment resistant schizophrenia (TRS). We discovered I as Clozapine-like dopamine D₂/D₁ receptor selectivity and improved reactive metabolites formation profile by the modification of piperazine moiety in Clozapine. The optimization of I gave compound II to be best compound (approx. 10-fold stronger affinity for D₂/D₁ receptor and similar D₂/D₁ selectivity ratio with Clozapine). Clozapine-like D₂/D₁ receptor occupancy profile was proved by in vivo evaluation. In addition, the reactive metabolites derived agranulocytosis risk of compound II was considered to be lower than Clozapine. The pharmacol. detail of compound II is being investigated to develop it for TRS treatment.

Bioorganic & Medicinal Chemistry Letters published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C9H10O4, Category: chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Watanabe, Hitoshi published the artcileIdentification of 2-fluoro-8-methyl-11-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepine with clozapine-like mixed activities at muscarinic acetylcholine, dopamine, and serotonin receptors, Category: chlorides-buliding-blocks, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 127911, database is CAplus and MEDLINE.

Identification of 2-fluoro-8-methyl-11-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepine with clozapine-like mixed activities at muscarinic acetylcholine, dopamine, and serotonin receptors. We hypothesized that brain penetration of NDMC differed from individual to individual, and highly permeable individuals may be responders, leading to M1 agonism. In order to demonstrate the Clozapine M1-hypothesis, we considered the following profile to be required: (i) robust M1 agonism, (ii) clozapine-like binding affinity toward various GPCRs, (iii) diminish or reduce reactive metabolite for-mation, (iv) no or weak M3 agonism, and (v) high brain permeability.

Bioorganic & Medicinal Chemistry Letters published new progress about 60091-87-4. 60091-87-4 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Nitro Compound,Carboxylic acid,Amine,Benzene, name is 2-((4-Chloro-2-nitrophenyl)amino)benzoic acid, and the molecular formula is C9H4F6O, Category: chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics