Synthesis and Evaluation of 4-Fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α2-Adrenoceptor

Grunewald, Gary L.; Caldwell, Timothy M.; Li, Qifang; Criscione, Kevin R.

doi:10.1021/jm010147g

Cited by 28 publications

(10 citation statements)

References 33 publications

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“…As shown in Scheme 9, it was found that the protection of the OH group with OSiMe 3 and NH with Boc was necessary, because the treatment of the unpro-tected secondary alcohol 48 with DAST gave 51 and 52 in <5% yields. 16…”

Section: Methodsmentioning

confidence: 99%

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds Using Deoxofluor and DAST

Singh¹,

Shreeve²

2002

Synthesis

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Selective fluorination of organic compounds continues to be a stimulating and exciting area of research. While a variety of fluorinating reagents and methodologies have been developed to fulfill the increasing demand for site selective fluorination of organic compounds, applications of Deoxofluor and DAST continue to be used widely. Our interest in applying synthetic methods for introducing fluorine or a fluorinated group into a large variety of organic compounds encouraged this review which highlights recent progress in fluorination reactions using Deoxofluor [bis(2-methoxyethyl)aminosulfur trifluoride] and DAST (diethylaminosulfur trifluoride) as key nucleophilic fluorinating reagents. This review covers the literature for fluorination reactions of organic com-

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Section: Methodsmentioning

confidence: 99%

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds Using Deoxofluor and DAST

Singh¹,

Shreeve²

2002

Synthesis

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“…Later, an improved purification was found by directly triturating the crude 19 / 20 in EtOAc to provide >98% purity 19 with a slightly better isolated yield (55%). The structure of the ring-contracted side product 20 was elucidated by HNMR and confirmed by X-ray diffraction studies, and a proposed mechanism for 20 is given in Scheme .…”

Section: Resultsmentioning

confidence: 93%

Process Development for Scale-Up of a Novel 3,5-Substituted Thiazolidine-2,4-dione Compound as a Potent Inhibitor for Estrogen-Related Receptor 1

Russell

Spink

et al. 2014

Org. Process Res. Dev.

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The development of a reproducible process for multihundred gram production of (Z)-5-((1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazol-5-yl)methylene)-3-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)thiazolidine-2,4-dione (26), a potent and selective inhibitor of estrogen-related receptor 1 (ERR1), is described. This multihundred gram synthesis was achieved via magnesium perchlorate-catalyzed regioselective epoxide ring-opening of tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (9) with thiazolidine-2,4-dione (6, TZD) to form a diastereomeric mixture tert-butyl 4-(2,4-dioxothiazolidin-3-yl)-3-hydroxypiperidine-1-carboxylate (17), of which the 3-hydroxyl group was functionally transformed to 3-fluoro derivative 19 after treatment with Deoxo-Fluor. Chiral separation of 19 provided the desired diastereomer (3R,4R)-21 that was converted to the secondary amine 23 TFA salt. Reductive amination of 23 produced the key intermediate N-methyl 24. Knoevenagel condensation of 24 with 1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazole-5-carbaldehyde (5) produced the final product 26 in 10% overall yield (99.7% HPLC area% with ≥99.5% de) after a convergent eight synthetic steps with the only column purification being the chiral HPLC separation of 3R,4R-21 from 3S,4S-22.

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“…37 Keto alcohols and trimethylsilyl-protected keto amino alcohols are reported to react with DAST to produce the corresponding monofluoro derivatives (eq 24). 38, 39 In the latter case, the ringcontracted product is also formed as the minor product.…”

Section: Miscellaneous Reactionsmentioning

confidence: 99%

Diethylaminosulfurtrifluoride

Fauq¹,

Singh²,

Meshri³

2006

Encyclopedia of Reagents for Organic Synthesis

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Synthesis and Evaluation of 4-Fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α₂-Adrenoceptor

Cited by 28 publications

References 33 publications

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds Using Deoxofluor and DAST

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds Using Deoxofluor and DAST

Process Development for Scale-Up of a Novel 3,5-Substituted Thiazolidine-2,4-dione Compound as a Potent Inhibitor for Estrogen-Related Receptor 1

Diethylaminosulfurtrifluoride

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Synthesis and Evaluation of 4-Fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α2-Adrenoceptor

Cited by 28 publications

References 33 publications

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds­ Using Deoxofluor and DAST

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds­ Using Deoxofluor and DAST

Process Development for Scale-Up of a Novel 3,5-Substituted Thiazolidine-2,4-dione Compound as a Potent Inhibitor for Estrogen-Related Receptor 1

Diethylaminosulfurtrifluoride

Contact Info

Product

Resources

About

Synthesis and Evaluation of 4-Fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α₂-Adrenoceptor

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds Using Deoxofluor and DAST

Recent Advances in Nucleophilic Fluorination Reactions of Organic Compounds Using Deoxofluor and DAST