Synthesis of 2,3,4,5-tetrahydro-1H-pyrrolo[1,2-a][1,4]diazepines and 11-methyl-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indoles

Katritzky, Alan R.; Jain, Ritu; Akhmedova, Rena G.; Xu, Yong‐Jiang

doi:10.3998/ark.5550190.0004.902

Cited by 6 publications

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References 13 publications

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“…We now report a direct and convenient procedure for the access of 4-hydroxy-11-iodo-2,3,4,5-tetrahydro [1,4]diazepino [1,2-a]indol-1-one skeleton (Scheme 2, Table 1) followed by the functionalisation of the position C-11 via palladium-mediated cross-coupling reactions.…”

Section: Figure 1 General Formulae Of I and Iimentioning

confidence: 99%

“…In summary, we developed an efficient and straightforward route to original 4-hydroxy-11-iodo-2,3,4,5-tetrahydro [1,4]diazepino [1,2-a]indol-1-one derivatives. Several substituents on position C-11 were introduced by Suzuki, Sonogashira and Heck reactions.…”

Section: Scheme 1 Retrosynthetic Scheme For the Synthesis Of IImentioning

confidence: 99%

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An efficient route to prepare the 4-hydroxy-2,3,4,5-tetrahydro [1,4]diazepino [1,2-a]indol-1-one scaffold is described. The key reactions of the synthesis are an iodolactonisation followed by a lactone-to-lactam rearrangement.

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confidence: 99%

“…Syntheses and reactivities of 1,4-diazepines fused with five-and six-membered heterocyclic rings are well investigated. 1 2,3,4,5-Tetrahydro [1,4]diazepino [1,2-a]indol-1one derivatives have received much less attention. One series of compounds I has been reported as precursor of serotonine antagonists (Figure 1).…”

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General and Easy Access to 11-Substituted 4-Hydroxy-2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-one Derivatives

Putey¹,

Fournet²,

Joseph³

2006

Synlett

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-S u b s t i t u t e d 4 -H y d r o x y -2 , 3 , 4 , 5 -t e t r a h y d r o [ , 4 ] d i a z e p i n o [ , 2 -a ] i n d o l e --o n e sAbstract: An efficient route to prepare the 4-hydroxy-2,3,4,5-tetrahydro [1,4]diazepino[1,2-a]indol-1-one scaffold is described. The key reactions of the synthesis are an iodolactonisation followed by a lactone-to-lactam rearrangement. Various 11-substituted derivatives were obtained by palladium-mediated cross-coupling reactions.Syntheses and reactivities of 1,4-diazepines fused with five-and six-membered heterocyclic rings are well investigated. 1 2,3,4,5-Tetrahydro[1,4]diazepino[1,2-a]indol-1-one derivatives have received much less attention. One series of compounds I has been reported as precursor of serotonine antagonists ( Figure 1). 2,3 The synthesis of I is achieved by ring closure of ethyl 1-(3-aminopropyl)-3-substituted-indole-2-carboxylates. 3As a part of an ongoing research work dedicated to the design of kinase inhibitors, we became interested in the design of new derivatives II. The retrosynthetic approach of this series was based on an iodolactonisation of 1-allylindole-2-carboxylic acids followed by a lactone-to-lactam rearrangement as shown in Scheme 1. Figure 1 General formulae of I and IIWe now report a direct and convenient procedure for the access of 4-hydroxy-11-iodo-2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-one skeleton (Scheme 2, Table 1) followed by the functionalisation of the position C-11 via palladium-mediated cross-coupling reactions.The esters 1 were synthesised by adapting standard methods. Compounds 1a 4 and 1b were prepared from esterification of the commercially available acids in 92-98% yield. Treatment of commercially available p-anisaldehyde with ethyl azidoacetate in the presence of MeONa yielded the azidoacrylate, which was converted into indole 1c by refluxing in xylene (overall yield 68%). 5 N-Allylation of indolic nitrogen 1 was carried out in the presence of allyl bromide and an appropriate base such as K 2 CO 3 or NaH to afford 2 in good yield (2a: 94%, 2b: 94% and 2c: 88%). Saponification of esters 2 afforded acids 3 in 96-100% yield. Scheme 1 Retrosynthetic scheme for the synthesis of IIThe iodolactonisation was investigated on model compound 3a. The first reaction conditions using iodine (2 equiv) in CHCl 3 -H 2 O at 0°C for 90 minutes afforded compound 4a in 66% yield. 6 Iodination of the position C-3 of the indole part occurred in the same time. Increase of the temperature reaction at 70°C afforded 4a in a better yield (84%). The second assay was performed on 3a in the presence of N-iodosuccinimide (2.3 equiv) and 2,6-lutidine in CH 2 Cl 2 at -20°C. 7 Compound 4a was again obtained in good yield (81%). 8 Iodolactonisation using Niodosuccinimide was applied to 3b and 3c to afford 4b and 4c, respectively, in 94% and 67% yield. The treatment of 3c with iodine at 0°C afforded 4c in a disappointing 15% yield. In this case, 1-allyl-2,3-diiodo-6-methoxyindole was isolated as the major product (41%).Lactones 4 were finally converted in...

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Section: Figure 1 General Formulae Of I and Iimentioning

confidence: 99%

Section: Scheme 1 Retrosynthetic Scheme For the Synthesis Of IImentioning

confidence: 99%

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