A Synthesis of Highly Functionalized Pyrido[2,1-d][1,2,5]triazepines

Abstract

A synthesis of functionalized 1-(alkylamino)-4-aryl-2,3-dihydro-2-phenylpyrido[2,1-d][1,2,5]triazepines from the sequential reaction between pyridinium ylides, alkyl isocyanides, and 1-[chloro(aryl)methylene]-2-phenylhydrazines in CH₂Cl₂, in good yields, is described.

Keywords

pyrido[2,1-d][1,2,5]triazepine - hydrazonoyl chloride - alkyl isocyanide - pyridinium ylide - MCR

References and Notes

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15

General Procedure for the Synthesis of Compound 4
To a suspension of 1 (1 mmol) and isocyanide 2 (1 mmol) in CH₂Cl₂ (4 mL) was added Et₃N (2 mmol) at r.t. After stirring for 20 h at r.t., hydrazonoyl chloride 3 (1 mmol) was added to the solution and stirred for 10 h. Subsequently, the solvent was evaporated, and the crude product was washed with EtOAc. The solid mixture was dissolved in CH₂Cl₂ (5 mL) and washed with two 3 mL portions of H₂O, then dried (Na₂SO₄), and evaporated under reduced pressure.
Selected Spectroscopic Data for Compound 4a
Pale yellow powder, mp 148-150 ˚C, yield 0.34 g, 90%. IR (KBr): ν_max = 3419 (NH), 1658, 1548, 1442 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 1.08 (3 H, t, ^³ J = 7.1 Hz, Me), 1.21 (9 H, s, CMe₃), 4.14-4.15 (2 H, m, CH₂O), 6.91 (1 H, t, ^³ J = 7.4 Hz, CH), 7.25-7.30 (4 H, m, 4 CH), 7.35-7.38 (2 H, m, 2 CH), 7.60-7.62 (2 H, d, ^³ J = 7.7 Hz, 2 CH), 7.79 (1 H, t, ^³ J = 6.4 Hz, CH), 7.93 (1 H, t, ^³ J = 6.4 Hz, CH), 8.48 (1 H, t, ^³ J = 8.1 Hz, CH), 8.73 (1 H, d, ^³ J = 6.4 Hz, CH), 8.85 (1 H, d, ^³ J = 6.4 Hz, CH), 9.59 (1 H, br s, NH), 10.32 (1 H, br s, NH) ppm. ^¹³C NMR (125.7 MHz, CDCl₃): δ = 13.9 (Me), 29.9 (CMe₃), 54.7 (C), 60.3 (CH₂O), 105.4 (C), 113.8 (2 CH), 121.0 (2 CH), 124.9 (C), 126.9 (CH), 127.1 (CH), 128.5 (CH), 128.7 (2 CH), 128.9 (2 CH), 130.9 (C), 135.0 (C), 143.8 (CH), 147.2 (CH), 147.5 (C), 148.3 (CH), 153.2 (C), 164.2 (C=O) ppm. MS: m/z (%) = 442 (4) [M⁺], 411 (75), 355 (77), 290 (28), 77 (100). Anal. Calcd (%) for C₂₇H₃₀N₄O₂ (442.24): C, 73.28; H, 6.83; N, 12.66. Found (%): C, 72.84; H, 6.51; N, 12.92.