Isoprene-Mediated Lithiation of 1-Alkylimidazoles: Chiral Induction of the Alkyl Substituent

Pastor, Isidro M.; Torregrosa, Rosario; Yus, Miguel

doi:10.2174/157017810791514850

Cited by 4 publications

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“…21,26 The Heinrich Debus method for the synthesis of imidazole ring from primary amines is widely reported in the literature. 22,27,28 However, its application to aminosteroids has not been reported.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The cyclization of 9 into 3α-imidazole (5) was achieved by reacting with aq. ammonia, formaldehyde, and glyoxal at 70 °C for 5 h. 27 As in the case of amine, the imidazole product was also isolated by acid base workup and further purified by passing through a plug of silica using 1−5% methanol in ethyl acetate. The pure product obtained was reprocessed with acid−base to obtain solvent free product in 71% yield.…”

Section: Organic Process Research and Developmentmentioning

confidence: 99%

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Improved Procedures for Gram-Scale Synthesis of Galeterone 3β-Imidazole and Galeterone 3β-Pyridine Methoxylate, Potent Androgen Receptor/Mnk Degrading Agents

Purushottamachar

Murigi

Njar

2016

Org. Process Res. Dev.

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Galeterone (1) and its C-3 analogs are of substantial interest because of their multitarget anticancer activities, including AR and Mnk degrading activities. Here, we describe improved and efficient procedures for the gram-scale synthesis of 3β-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (galeterone 3β-imidazole, 2) and 3β-(pyridine-4-ylmethoxy)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (galeterone 3β-pyridine methoxylate, 3). Whereas compound 2 was synthesized in 63% overall yield from galeterone (1) over four steps, via key intermediate, 3β-azido galeterone (8); compound 3 was synthesized in 61% overall yield from 1 in one step. This article also reports on the facile synthesis of other potential AR/Mnk degrading agents (ARDAs/MNKDAs), including galeterone 3α-imidazole (5) and galeterone 3β-amine (10), both in excellent overall yields. Notably, except for the one-step synthesis of compound 3 which required purification by flash column chromatography, none of the intermediates and target compound 2 required extensive chromatographic purifications or multiple crystallizations.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Organic Process Research and Developmentmentioning

confidence: 99%

Improved Procedures for Gram-Scale Synthesis of Galeterone 3β-Imidazole and Galeterone 3β-Pyridine Methoxylate, Potent Androgen Receptor/Mnk Degrading Agents

Purushottamachar

Murigi

Njar

2016

Org. Process Res. Dev.

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“…13 In this paper, we report the application of the isoprene-mediated lithiation process for the preparation of imidazole derivatives bearing a primary or secondary alkyl substituent on the nitrogen. 14…”

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confidence: 99%

“…13 C NMR (100 MHz, CDCl 3 ): δ = 13.4, 19.7, 32.2, 46.6, 76.2 (q, J = 29.8 Hz), 122.0, 124.2 (q, J = 286 Hz), 127.0, 127.2, 128.4, 129.1, 136.0, 143.7. MS (DIP, EI): m/z (%) = 299 (10) [M + + 1], 298 (27) [M + ], 297 (10), 269 (28), 256 (11), 251(14), 241(12), 230(15), 229 (90), 199 (60), 187(10), 173 (100), 165(17), 149 (13), 144(10), 133(10), 123(11), 117(10), 105 (51), 95 (39), 91(18), 77 (34), 69(10), 57(11), 55 (10), 43(15), 41(14).HRMS: m/z [M + ] calcd for C 15 H 17 F 3 N 2 O: 298.1293; found: 298.1289.…”

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confidence: 99%

Isoprene as Lithiation Mediator: Synthesis of 2-Substituted 1-Alkylimidazole Derivatives

et al. 2012

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The lithiation of different imidazoles bearing a primary (i.e., butyl, pentyl, dodecyl) or secondary (i.e., cyclohexyl, 1-methylheptyl) alkyl substituent on the nitrogen has been successfully achieved by means of an isoprene-mediated protocol. The subsequent reaction of the 2-lithioimidazole intermediates with different electrophiles leads to the formation of interesting 1,2-disubstituted imidazoles.

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ChemInform Abstract: Isoprene‐Mediated Lithiation of 1‐Alkylimidazoles: Chiral Induction of the Alkyl Substituent.

2010

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Isoprene-Mediated Lithiation of 1-Alkylimidazoles: Chiral Induction of the Alkyl Substituent. -The isoprene-mediated lithiation of imidazoles (IV) bearing a secondary alkyl substituent at the nitrogen and subsequent nucleophilic addition to aldehydes and ketones (V) allows the preparation of the corresponding 2-functionalized imidazoles (VI). In the presence of a stereogenic centre in the alkyl side chain moderate diastereoselectivity is observed. -(PASTOR*, I. M.; TORREGROSA, R.; YUS, M.; Lett. Org. Chem. 7 (2010)

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Isoprene-Mediated Lithiation of 1-Alkylimidazoles: Chiral Induction of the Alkyl Substituent

Cited by 4 publications

References 0 publications

Improved Procedures for Gram-Scale Synthesis of Galeterone 3β-Imidazole and Galeterone 3β-Pyridine Methoxylate, Potent Androgen Receptor/Mnk Degrading Agents

Improved Procedures for Gram-Scale Synthesis of Galeterone 3β-Imidazole and Galeterone 3β-Pyridine Methoxylate, Potent Androgen Receptor/Mnk Degrading Agents

Isoprene as Lithiation Mediator: Synthesis of 2-Substituted 1-Alkylimidazole Derivatives

ChemInform Abstract: Isoprene‐Mediated Lithiation of 1‐Alkylimidazoles: Chiral Induction of the Alkyl Substituent.

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