Late Stage CH Activation of a Privileged Scaffold; Synthesis of a Library of Benzodiazepines

Abstract

This paper is dedicated to Professor MichelP feffer (ULP,S trasbourg) for his contributions to C À Ha ctivation and palladacycle chemistry. Abstract: Al ibrary of over twenty 5-(2-arylphenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-ones has been formed by am icrowave-mediated late-stage palladium-catalysed arylation of 1,4-benzodiazepines using diaryliodonium salts. This can also be applied to nordazepam (7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one), the active metabolite of diazepam, and subsequent N-alkylation and/or H/D exchangea llowsf urther diversification towards elaborated pharmaceuticals andt heir3 ,3'-deuterated analogues.

Synthesis and Characterisation of Transition Metal Complexes of a Novel 1,5‐benzodiazepine‐Functionalised Tertiary Phosphine

“…The C(21)À N(2) distance of 1.298(5) Å is similar to that observed in I [13] and other 1,5-benzodiazepines. [15] There is also a strong intramolecular O(1 [16] which manifests itself in the downfield OH resonance (δ 15.44) observed in the 1 H NMR spectrum of 1.…”

“…C 35 H 31 N 2 OP: M r = 526.59, orange plate, 0.15 × 0.15 × 0.05 mm 3 , monoclinic, space group Cc, a = 21.7254(4), b = 9.3204(4), c = 17.2585(7) Å, α = 90, β = 128.8516(15), γ = 90°, V = 2759.39(18) Å 3 , T = 100(2) K, Z = 4, λ = 0.71073 Å, μ(Mo-Κ α ) = 0.13 mm À 1 , θ range for data collection = 3.0-27.5°, 5108 independent reflections measured, R int = 0.051, d calc = 1.268 g cm À 3 , R1 = 0.050 (for 4274 data with I > 2σ(I)), wR2 = 0.130 (for all data), and 357 refined parameters, largest difference map features between 0.42and À 0.35 e/Å 3 . Crystal data for 2 a • Et 2 O: C 45 H 46 Cl 2 IrN 2 OP • C 4 H 10 O: M r = 999.02, yellow needle, 0.20 × 0.06 × 0.05 mm 3 , monoclinic, space group P2 1 /c, a = 8.5317(17), b = 31.083(6), c = 16.757(3) Å, β = 94.04(3)°, V = 4432.8(15) Å 3 , T = 100(2) K, Z = 4, λ = 0.71073 Å, μ(Mo-Κ α ) = 3.21 mm À 1 , θ range for data collection = 3.1-22.5°, 4811 independent reflections measured, R int = 0.149, d calc = 1.497 g cm À 3 , R1 = 0.067 (for 3161 data with I > 2σ(I)), wR2 = 0.134 (for all data), and 515 refined parameters, largest difference map features between 1.33 and À 1.20 e/Å 3 .…”

Recent Developments in Microwave-Assisted Metal-Catalyzed C–H Functionalization of Heteroarenes for Medicinal Chemistry and Material Applications

“…It should be noted that only one example of intramolecular C-H arylation is described and it is related to the synthesis of isochroman derivatives. 26 In parallel, the palladium-catalyzed C-H arylation of the aryl group of bi(het)aryl compounds is also reported and gives access to compounds such as materials for organic light-emitting diodes 27 and benzodiazepine 28 derivatives.…”

Deliberately Losing Control of C−H Activation Processes in the Design of Small‐Molecule‐Fragment Arrays Targeting Peroxisomal Metabolism

“…[2][3][4][5][6][7][8][9][10][11][12][13][14] We have recently disclosed our findings on the microwave mediated ortho-CÀ H activation of benzodiazepines using iodonium salts under Pd catalysis ( Figure 1). [15] These processes tend to give monoarylated products although, under more forcing conditions, a second ortho-arylation was observed. Recent, complementary, studies on the visible light mediated "Sanford" arylation [16][17][18] of benzodiazepines using diazonium salts and dual Ru/Pd catalysis led mainly to mono-functionalised product.…”