The development of a short route to the API ropinirole hydrochloride

Yousuf, Zeshan; Richards, Andrew K.; Dwyer, Andrew N.; Linclau, Bruno; Harrowven, David C.

doi:10.1039/c5ob01739d

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…Tarur Harrowven et al reported two ways of ropinirole synthesis involving the reductive alkylation of bis-n-propylamine. 162 A reaction of n-Pr 2 NH with aldehyde 2.29.b in the presence of 2.3 equiv of sodium cyanoborohydride quantitatively furnished amine 2.29.c (6.7 g, 49% RME), which can be converted to ropinirole (Scheme 79).…”

Section: Galanthaminementioning

confidence: 99%

Reductive Amination in the Synthesis of Pharmaceuticals

et al. 2019

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Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among biologically active compounds. It is one of the key approaches to C–N bond construction due to its operational easiness and a wide toolbox of protocols. Recent studies show that at least a quarter of C–N bond-forming reactions in the pharmaceutical industry are performed via reductive amination. This Review concisely compiles information on 71 medical substances that are synthesized by reductive amination. Compounds are grouped according to the principle of action, which includes drugs affecting the central nervous system, drugs affecting the cardiovascular system, anticancer drugs, antibiotics, antiviral and antifungal medicines, drugs affecting the urinary system, drugs affecting the respiratory system, antidiabetic medications, drugs affecting the gastrointestinal tract, and drugs regulating metabolic processes. A general synthetic scheme is provided for each compound, and the description is focused on reductive amination steps. The green chemistry metric of reaction mass efficiency was calculated for all reactions.

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Section: Galanthaminementioning

confidence: 99%

Reductive Amination in the Synthesis of Pharmaceuticals

et al. 2019

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“…We investigated the viability of the methodology on other naphthalene derivatives, in particular 1-aminonapthalene 1b which is of interest because of its use in the synthesis of the API Ropinirole·HCl, developed by Harrowven and co-workers ( Figure 5 a). 56 The reduction product 2b was formed with high yield and selectivity, with only a trace of the over-reduction product, 5-aminotetralin, present. A sample (100 mL) was collected once the reactor was at the steady state, which was worked up to give an isolated yield of 95% for 2b which equates to a projected productivity for 2b of 114 g day –1 (782 mmol day –1 ).…”

Section: Resultsmentioning

confidence: 97%

“…13 1-Amino-5,8-dihydronapthalene 2b. 57 Isolated as a reddish solid. 1 The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.oprd.2c00108.…”

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confidence: 99%

High-Productivity Single-Pass Electrochemical Birch Reduction of Naphthalenes in a Continuous Flow Electrochemical Taylor Vortex Reactor

Lee

Love

Mansouri

et al. 2022

Org. Process Res. Dev.

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We report the development of a single-pass electrochemical Birch reduction carried out in a small footprint electrochemical Taylor vortex reactor with projected productivities of >80 g day –1 (based on 32.2 mmol h –1 ), using a modified version of our previously reported reactor [ Org. Process Res. Dev. 2021 , 25 , 7, 1619–1627], consisting of a static outer electrode and a rapidly rotating cylindrical inner electrode. In this study, we used an aluminum tube as the sacrificial outer electrode and stainless steel as the rotating inner electrode. We have established the viability of using a sacrificial aluminum anode for the electrochemical reduction of naphthalene, and by varying the current, we can switch between high selectivity (>90%) for either the single ring reduction or double ring reduction with >80 g day –1 projected productivity for either product. The concentration of LiBr in solution changes the fluid dynamics of the reaction mixture investigated by computational fluid dynamics, and this affects equilibration time, monitored using Fourier transform infrared spectroscopy. We show that the concentrations of electrolyte (LiBr) and proton source (dimethylurea) can be reduced while maintaining high reaction efficiency. We also report the reduction of 1-aminonaphthalene, which has been used as a precursor to the API Ropinirole. We find that our methodology produces the corresponding dihydronaphthalene with excellent selectivity and 88% isolated yield in an uninterrupted run of >8 h with a projected productivity of >100 g day –1 .

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“…We envisaged that water might act as a nucleophile to promote this transformation. Therefore, we conducted the reaction in t BuOH/H 2 O = 9:1, which gave 5a and 5b in 93 % and 58 % yield respectively. Interestingly, substrate bearing amide group, such as 3‐(5‐bromo‐1 H ‐indol‐3‐yl)propanamide 4c also led to 5a in 57 % yield, which revealed that the reaction proceeded via nucleophilic attack of oxygen on amide and followed by hydrolysis of imine intermediate (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Hypervalent Iodine‐Mediated Cyclization of Homotryptamine Derivatives

et al. 2019

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A facile and efficient cyclization of homotryptamines and their derivatives has been established for the construction of 4a‐chlorotetrahydropyrido[2,3‐b]indoles and 3,3‐spirocyclic 3H‐indoles using hypervalent iodine (1‐chloro‐1,2‐benziodoxol‐3‐one) under mild conditions. The broad substrate scope and successful gram‐scale experiment grant this metal‐free transformation great potential for further application.

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The development of a short route to the API ropinirole hydrochloride

Cited by 6 publications

References 26 publications

Reductive Amination in the Synthesis of Pharmaceuticals

Reductive Amination in the Synthesis of Pharmaceuticals

High-Productivity Single-Pass Electrochemical Birch Reduction of Naphthalenes in a Continuous Flow Electrochemical Taylor Vortex Reactor

Hypervalent Iodine‐Mediated Cyclization of Homotryptamine Derivatives

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