Author: tianli

Syntheses in the phenanthrene series. VI. Synthesis of morphinane was written by Grewe, Rudolf;Mondon, Albert. And the article was included in Chemische Berichte in 1948.Quality Control of 3-Chloro-5,6,7,8-tetrahydroisoquinoline This article mentions the following:

Et cyclohexanone-2-carboxylate (225 g.), 170 g. NCCH₂CO₂Et, 23 g. NH₄OAc, 72 g. AcOH, and 300 cc. C₆H₆ are refluxed 6-7 hrs. at 160° with simultaneous separation of the H₂O formed (45 cc.). After addnl. heating for 1 hr., 200 cc. ether is added to the cooled mixture, the ether layer washed with NaHCO₃ and H₂O, and the ether evaporated Distillation of the residue gives 75% 1,2-C₆H₉(CO₂Et):C(CN)CO₂Et (I), b₁ 160-70°, b_0.3 155°, in addition to a small amount of Et tetrahydroanthranilate, m. 73.5°. I (300 g.) is refluxed 7 hrs. with 1.2 l. concentrated HCl with stirring and, after addition of 300 cc. more HCl, another 2 hrs., giving 73% 2-carboxy-1-cyclohexene-1-acetic acid (II), m. 165°. The mother liquor is concentrated over the free flame until the crystallization of NH₄Cl begins, neutralized with NaHCO₃, and 12% 1,3-dihydroxy-5,6,7,8-tetrahydroisoquinoline (III), m. 205°, is filtered off. An intimate mixture of 140 g. II and 250 g. (NH₄)₂CO₃ is slowly heated in an oil bath at 230° until the NH₃ evolution has ceased, giving 92% III, pale yellow crystalline powder from 70% AcOH. Heating 115 g. III and 200 cc. POCl₃ 3 hrs. at 200°, pouring the reaction mixture onto ice, and distilling the reaction product give 95% 1,3-dichloro-5,6,7,8-tetrahydroisoquinoline (IV), b_0.8 134°, crystals from EtOH, m. 87°, insoluble in dilute HCl, volatile with steam. Reduction of IV in EtOH with Raney Ni in the presence of 2 equivalents Na in EtOH at 50° and 80 atm. gives 100% 5,6,7,8-tetrahydroisoquinoline (V). V is also obtained in 83% yield on addition of 75 g. Raney Ni in small portions over a period of 0.5 hr. to 20 g. IV in 600 cc. 10% NaOH at 90°, or in 100% yield by addition of 100 g. Zn dust to 60 g. IV in 400 cc. concentrated HCl at not over 40° with vigorous stirring, concentrating the reaction mixture over a free flame, making it strongly alk. while warm, and extracting it with ether, giving the 3-mono-Cl analog (VI) of IV, b₁₃ 143°, which is reduced with H in the presence of Pd-charcoal, thus giving 100% V, b₁₂ 102-4° (picrate, yellow leaflets, m. 144°). To V.MeI is added 1.6 mols. PhCH₂MgCl in ice-cold ether; after the exothermic reaction is over, the product is decomposed with NH₄Cl and extracted with ether, giving 83% 2-methyl-1-benzyl-1,2,5,6,7,8-hexahydroisoquinoline (VII), b_0.3 128-30°. VII readily decompose and gives no crystalline derivatives Hydrogenation of VII in N HCl with Adams catalyst gives 93% of the 1,2,3,4,5,6,7,8-octahydro derivative (VIII), b_0.5 136° (picrate m. 134°). Heating 33.6 g. VIII with 336 g. H₃PO₄ (d. 1.7) 3 days at 150° and extracting the diluted and alkalized mixture with ether give 50% N-methylmorphinane (IX), crystals from petr. ether (b. 30-60°), m. 61°. IX can also be isolated as the picrate, golden yellow leaflets, m. 174°. From the mother liquor 2 isomeric IX picrates, m. 203° and 201°, are isolated. IX.HCl m. 231-3°; IX sulfate m. 205°; IX.MeI (X) m. 253°. Heating 1.5 g. X with 10% NaOH gives 95% of the des-base (XI), an oil (picrate m. 217°). Dehydrogenation of 0.7 g. XI with 0.2 g. Pd-charcoal 0.5 hr. at 320° gives 80% phenanthrene, m. 97-8° (picrate m. 143°). Cyclization of 3 g. of the carbinol base (XII) as described earlier (4b-(2-dimethylaminoethyl)-4b,5,6,7,8,8a,9,10-octahydrophenanthrene (XIII), b_0.2 150° (picrate m. 185°). Hydrogenation of XI with PtO₂ catalyst gives XIII (picrate m. 185°). Refluxing 3.5 g. IX with 2 g. BrCN in CHCl₃ gives 2 g. N-cyanomorphinane (XIV), b_0.05 162°, fine needles, m. 104°. Refluxing 1 g. XIV with 6 N HCl until a sample remains clear on addition of H₂O gives 0.7 g. morphinane (XV), b_0.05 115° (HCl salt m. 229°; sulfate m. 195°; picrate m. 207°). Methylation of XV with MeI and NaOH gives X, m. 251°. In the experiment, the researchers used many compounds, for example, 3-Chloro-5,6,7,8-tetrahydroisoquinoline (cas: 875249-27-7Quality Control of 3-Chloro-5,6,7,8-tetrahydroisoquinoline).

3-Chloro-5,6,7,8-tetrahydroisoquinoline (cas: 875249-27-7) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity.Quality Control of 3-Chloro-5,6,7,8-tetrahydroisoquinoline

Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Visible Light-Driven α-Alkylation of N-Aryl tetrahydroisoquinolines Initiated by Electron Donor-Acceptor Complexes was written by Xia, Qing;Li, Yufei;Wang, Xinmin;Dai, Peng;Deng, Hongping;Zhang, Wei-Hua. And the article was included in Organic Letters in 2020.Electric Literature of C11H16ClNO2 This article mentions the following:

The visible light-driven α-alkylation of N-aryl tetrahydroisoquinolines was initiated through electron donor-acceptor complex photochem. The reaction can proceed smoothly without the addition of any photocatalysts, transition-metal catalysts, or addnl. oxidants. The proposed mechanism was supported by various mechanistic studies, and the reactive open-shell alkyl radicals were generally produced from an alkylamine and underwent radical coupling for alkylating a wide range of N-aryl tetrahydroisoquinolines. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Electric Literature of C11H16ClNO2).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. Tetrahydroisoquinoline derivatives may be formed in the body as metabolites of some drugs, and this was once thought to be involved in the development of alcoholism.This is no longer generally accepted by the scientific community.Electric Literature of C11H16ClNO2

Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

The Discovery of Capsazepine, the First Competitive Antagonist of the Sensory Neuron Excitants Capsaicin and Resiniferatoxin was written by Walpole, Christopher S. J.;Bevan, Stuart;Bovermann, Guenter;Boelsterli, Johann J.;Breckenridge, Robin;Davies, John W.;Hughes, Glyn A.;James, Iain;Oberer, Lukas. And the article was included in Journal of Medicinal Chemistry in 1994.Name: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride This article mentions the following:

Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. Conformationally constrained analogs I [R¹ = OH, OMe, H; R² = OH, OMe; R³ = H, OH; R⁴ = octyl, 4-ClC₆H₄CH₂CH₂; n = 1-3] of these mols. were prepared The resulting compounds provided agonists of comparable potency to unconstrained analogs as well as a moderately potent antagonist, capsazepine (I, R¹ = R² = OH, R³ = H, R⁴ = 4-ClC₆H₄CH₂CH₂, n = 3). This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Name: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. In particular, 1-benzyl1,2,3,4-tetrahydroisoquinolines are dopamine receptor antagonists. An oxidative C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents is mediated by diethyl azodicarboxylate (DEAD). This C-H activation under metal-free conditions delivers target compounds, including some naturally occurring alkaloids, in good yields.Name: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride

Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex-vivo expansion was written by Feng, Yue;Xie, Xiao-Yang;Yang, Yi-Qiu;Sun, Yu-Tong;Ma, Wen-Hui;Zhou, Peng-Jun;Li, Zi-Yao;Liu, Hui-Qiang;Wang, Yi-Fei;Huang, Yun-Sheng. And the article was included in European Journal of Medicinal Chemistry in 2019.Synthetic Route of C11H16ClNO2 This article mentions the following:

The synthesis of pyrimidoindole analogs I [R = dimethylamino, 3-chloro-4-fluoroanilino, 3,4-dimethoxyphenthylamino, etc.] and II [R¹ = anilino, morpholino, indole-3-ethylamino, etc.] and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog I [R = 2-(6,7-dimethoxy-1,2,3,4-trtrahydroisoquinolino)ethylamino (III)] was found to be the most effective in stimulating ex-vivo expansion of UCB CD34⁺ cells and CD34⁺CD38^– cells. Initial data indicated that compound III promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with III retained adequate multi-lineage differentiation capacity. In addition, compound III was not cytotoxic at its test concentrations, suggested that it merits further investigation for potential clin. applications. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Synthetic Route of C11H16ClNO2).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. In particular, 1-benzyl1,2,3,4-tetrahydroisoquinolines are dopamine receptor antagonists. The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity.Synthetic Route of C11H16ClNO2

Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Chemical modification of tetrahydroisoquinoline and their cytotoxic activity was written by Terenteva, Ekaterina O.;Khashimova, Zaynat S.;Tsay, Elena A.;Zhurakulov, Sherzod N.;Saidov, Abdusalom Sh.;Vinogradova, Valentina I.;Azimova, Shakhnoz S.. And the article was included in Asian Journal of Pharmacy and Pharmacology in 2017.Electric Literature of C11H16ClNO2 This article mentions the following:

A variety of differently functionalized 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines I [R = H, Me, CH₂CH₂OH; R¹ = H, Ph, 1,3-benzodioxol-5-yl, etc.], bis tetrahydroisoquinolines II [X = (CH₂)₄, 1,3-phenylene, (CH₂)₁₁, etc.; R² = MeO, R²R² = OCH₂O] and chromanones III [R³ = 2-(1,3-benzodioxol-5-yl)ethylamino, 2-(3,4-dimethoxyphenyl)ethylamino, 6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl, etc.] were synthesized. Classic intramol. Bischler-Napieralski cyclodehydration was employed to generate the isoquinoline core. All the structures were characterized by NMR and mass spectrometry. The cytotoxic activities against three human cancer cell lines and primary culture of healthy hepatocyte cells were evaluated for all the synthesized compounds and structure-activity relationships were established by MTT assay. It was shown that compound I [R = H, R¹ = hexyl] was demonstrated selective cytotoxicity against breast adenocarcinoma (IC₅₀: 43.3 μM), I [R = H, R¹ = 6-chloro-1,3-benzodioxol-5-yl; R = Me, R¹ = 1,3-benzodioxol-5-yl] against laryngeal adenocarcinoma (IC₅₀: 18.0 and 2.3 μM resp.) with the absence of toxicity to healthy cells. Bis compounds II exhibited greater cytotoxic effect than mono-series compounds I. Among bis samples compound II [X = (CH₂)₁₁, R² = MeO] showed the greatest cytotoxic properties with an IC₅₀ value of 3.1-4.0 μM. The all conjugate compounds completely lacked cytotoxicity toward cancer cell lines and III [R³ = 2-(1,3-benzodioxol-5-yl)ethylamino, 6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl] demonstrated proliferative activity. The most promising compounds for further study in-vitro and in-vivo methods were dibasic compounds II [X = (CH₂)₇, (CH₂)₈; R² = MeO]. Later these substances can be offered as a basis for drugs with anti-tumor properties. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Electric Literature of C11H16ClNO2).

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.Electric Literature of C11H16ClNO2

Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem