Resonance-assisted amide protonation in dutasteride hydrochloride salt

Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Ravikumar, K.

doi:10.1039/c2ce06421a

Cited by 21 publications

(34 citation statements)

References 46 publications

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“…Non-planar amides have been frequently employed to investigate fundamental properties of amide bonds, such as proton exchange, 70–72 bonding, 128–131 rotational barriers, 76–77 chemical reactivity. 67–69 The effect of amide distortion has been leveraged to control chemical transformations 132–140 including hydrolysis, 61–66 acylation, 132–134 desymmetrization 135 and kinetic resolution 136,137 of alcohols.…”

Section: General Properties Of Bridged Lactamsmentioning

confidence: 99%

Chemistry of Bridged Lactams and Related Heterocycles

2013

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CONTENTS 1. Introduction 5702 2. General Properties of Bridged Lactams 5703 2.1. Distortion Parameters of Bridged Lactams 5703 2.2. Bond Lengths of Bridged Lactams 5703 2.3. Spectroscopic Properties of Bridged Lactams 5703 2.4. Analogy of Bridged Lactams to Bridgehead Olefins 5704 2.5. Chemical and Biological Significance of Distorted Amides 5704 3. Synthesis of Historically Important Bridged Lactams 5704 3.1. Quinuclidone Derivatives 5704 3.2. Adamantanone Derivatives 5707 4. Synthesis of Bridged Lactams with the N−(CO) Bond on a Two-Carbon or Larger Bridge, ([m. (≥2).n] Type) 5708 4.1. Condensation Reactions Forming the N− C(O) Bond 5708 4.2. Heck Reactions 5711 4.3. Diels−Alder Reactions 5712 4.4. Carbene Insertion Reactions 5713 4.5. Reactions via Radical Intermediates 5714 4.6. Miscellaneous Examples 5714 5. Synthesis of Bridged Lactams with the N−(CO) Bond on a One-Carbon Bridge, ([m.1.n] Type) 5715 5.1. Carbene Insertion Reactions 5715 5.2. Schmidt Reactions 5716 5.3.

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Section: General Properties Of Bridged Lactamsmentioning

confidence: 99%

Chemistry of Bridged Lactams and Related Heterocycles

2013

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“…20 Dutasteride layers are formed by the molecules creating a herringbone bond-like pattern with pairs of neighboring 'heads' of lactam groups (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…20 Dutasteride form I (Fig. 1) crystallizes in the P2 1 2 1 2 1 orthorhombic space group (as dutasteride hemihydrate) with one molecule in the asymmetric part of the unit cell.…”

Section: Resultsmentioning

confidence: 99%

Phase transition studies of dutasteride crystalline forms

et al. 2015

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Three crystalline forms of dutasteride, known in the literature as forms I, II and III, were studied. It has been proved that only form I is an unsolvated form. Both forms II and III are hydrates (pseudopolymorphs).Phase transition studies performed by thermoanalytical techniques and variable temperature PXRD measurements, in the temperature region from 30 to 180°C, revealed that dehydration leads to an unstable phase, which finally transforms into form I. Details of the crystal and molecular structure of form I are presented. Dutasteride form I crystallizes in the orthorhombic P2 1 2 1 2 1 space group with one molecule in the asymmetric part of the unit cell. Dutasteride molecules form a herringbone bond-like pattern with pairs of neighboring 'heads' of lactam groups.

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“…It has been shown that although organic amide functionalities are normally thought of as being non-basic, it is possible to protonate them using strong acids and even to isolate and characterise their salt forms in the solid state. [1][2][3] Such salt formation reactions are a staple of pharmaceutical form screening, where they are used to modify the physicochemical properties of basic Active Pharmaceutical Ingredients (APIs). [4] Whilst the acidic materials formed by protonating amides are unlikely to make commercially viable APIs, it has been suggested that access to such forms may confer substantial benefits during the manufacturing process.…”

Section: Introductionmentioning

confidence: 99%

“…[5] In 2012 Nanubolu et al collated the then known crystal structures of a variety of protonated amides. [2] Since then several groups have crystallographically investigated series of multiple salt forms of particular amide APIs, notably the paracetamol work already mentioned above and structures of the model APIs carbamazepine (CBZ) and its congener dihydrocarbamazepine (DCBZ). [1,[6][7][8] The interest in looking at multiple related structures rather than single salt forms is of course the increased ability to compare and contrast both structures and the properties that arise from these structures.…”

Section: Introductionmentioning

confidence: 99%

Structural study of salt forms of amides; paracetamol, benzamide and piperine

Kennedy

King

Oswald³

et al. 2018

Journal of Molecular Structure

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Single crystal x-ray diffraction has been used to investigate the structures of six complexes containing O-atom protonated cations derived from the pharmaceutically relevant amides benzamide (BEN), paracetamol (PAR) and piperine (PIP). The structures of the salt forms [PAR(H)][SO3C6H4Cl], [BEN(H)][O3SC6H4Cl] and [BEN(H)][Br].H2O are reported along with those of the hemi-halide salt forms [PAR(H)][I3].PAR , [PIP(H)][I3].PIP and [PIP(H)][I3]0.5[I]0.5.PIP. The structure of the cocrystal BEN.HOOCCH2Cl is also presented for comparison. The geometry of the amide group is found to systematically change upon protonation, with the C=O distance increasing and the C-N distance decreasing. The hemi-halide species all feature strongly hydrogen bonded amide(H)/amide pairs. The amide group C=O and C-N distances for both elements of each such pair are intermediate between those found for simple neutral amide and protonated amide forms. It was found that crystallising paracetamol from aqueous solutions containing Ba2+ ions gave orthorhombic paracetamol

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Resonance-assisted amide protonation in dutasteride hydrochloride salt

Cited by 21 publications

References 46 publications

Chemistry of Bridged Lactams and Related Heterocycles

Chemistry of Bridged Lactams and Related Heterocycles

Phase transition studies of dutasteride crystalline forms

Structural study of salt forms of amides; paracetamol, benzamide and piperine

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