Selective C-Acylation of 2-Aminoimidazo[1,2-a]pyridine: Application to the Synthesis of Imidazopyridine-Fused [1,3]Diazepinones

Abstract

A series of 20 optically pure 3,4-dihydro-5H-pyrido[1',2':1,2]imidazo[4,5-d][1,3]diazepin-5-ones which form a new family of azaheterocycle-fused [1,3]diazepines were synthesized in four steps with 17-66% overall yields. The key step consists of a selective C-acylation reaction of easily accessible 2-aminoimidazo[1,2-a]pyridine at C-3.

Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity

“…Compounds 2a 13 , 2c-d 14 , 2f-g 14 , 3i 14 , JMV5038 13 , Boc-azidonorleucine 29 15 and compound 23 11 were synthesised according to previous reported procedures and their physical characteristics were in agreement with the published data.…”

“…To a suspension of trifluoro-N-imidazo[1,2-a]pyridin-2-acetamide 13 (0.5 g, 2.18 mmol) in 5 N aqueous sodium hydroxide (9 ml), was added THF (0.5 ml). The solution was stirred at 40 C for 2 h. The solution was extracted with dichloromethane (3 Â 20 ml).…”

“…Pyrido-imidazodiazepinones 4-20 were synthesised starting from 2-amino-imidazo[1,2-a]pyridine 1, by selective C-3 acylation of the imidazo[1,2-a]pyridine nucleus (Scheme 1), using 9 different N-Boc amino-acids (Boc-Ala-OH, Boc-Nle-OH, Boc-Leu-OH, Boc-Asp(Bn)-OH, Boc-Pra-OH, S or R Boc-Lys(Cbz)-OH, Boc-6-azido-Nle-OH or Boc-Pro-OH), according to our previously reported methodology 10,11,13,14 . C-3 acylated compounds 2a-i were isolated in 36-97% yield after chromatography on alumina gel.…”

Inhibitors of kallikrein‐related peptidases: An overview

“…Recently, we reported a new series of heterocyclic compounds, based on the pyrido-imidazodiazepinone scaffold as competitive and reversible inhibitors of KLK7. [139][140][141] Among the synthesized derivatives, compound 13 (Fig. 18) showed the most potent inhibitory activity (K i = 27 M).…”

Synthesis of Thieno[3,2‐e][1,4]diazepin‐2‐ones: Application of an Uncatalysed Pictet–Spengler Reaction

“…[3][4][5][6] Since the discovery of benzodiazepines as central nervous system depressants, many synthetic derivatives that display a wide range of therapeutic applications in antithrombotic, [7] antibiotic, [8] and antitumor [9,10] areas, have been extensively developed. [19,20] We also investigated the thiophene isoster (namely thieno- [1,4]diazepine) scaffold. [17,18] Recently, we focused our efforts on the development of a new azaheterocycle-fused [1,3]diazepine scaffold and successfully reported on the synthesis of the first series of imidazopyridine-fused [1,3]diazepinones.…”