Yield:20934-50-3 75%

Reaction Conditions:

with sodium tetrahydroborate in tetrahydrofuran at 50; for 1 h;

Steps:

1-Methyl-3,4-dihydroquinoxalin-2(1H)-one 1

To a stirred suspension of cyanoacetic acid (2.2 g, 26 mmol) in CH₂Cl₂ (100 mL) at 0 °C was added oxalyl chloride (2.0 mL, 24 mmol), followed by N,N-dimethylformamide (12 drops) and the mixture was warmed to room temperature (rt). After 3 h, N-methylaniline (2.2 mL, 20 mmol) in CH₂Cl₂ (80 mL) was added, followed by dropwise addition of trimethylamine (7.0 mL, 70 mmol) at 0 °C. The mixture was warmed to rt and stirred for 17 h. Water (40 mL) was added and the organic layer was separated, was washed with aqueous HCl (40 mL, 1 M), and was dried (MgSO₄), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel,eluting with petrol-EtOAc (1:1), gave the amide A (3.4 g, 98%) as an amorphous solid; m.p. 74-76 °C (lit.¹ 76-79 °C); ¹H NMR (400 MHz, CDCl₃) δ = 7.58-7.39 (3H, m, 3 × CH), 7.33-7.20 (2H, m, 2 × CH), 3.34 (3H, s, CH₃), 3.25 (2H, s, CH₂); ¹³C NMR (100 MHz, CDCl₃) δ = 161.7, 142.4, 130.5, 129.1, 127.1, 114.1, 37.9, 25.4. Data consistent with the literature.¹ To a stirred solution of amide A (1.0 g, 5.7 mmol) in MeCN (29 mL) was added tert-butyl nitrite (3.5 mL, 29 mmol), Cs₂CO₃ (3.7 g, 12 mmol), glacial acetic acid (1.6 mL, 29 mmol) and 4 ? MS (2.9 g). The mixture was stirred at 100 °C for 6 h. Na₂S₂O₄ (3.5 g, 20 mmol) in a mixture of EtOH (57 mL) and water (115 mL) was added and the mixture was heated for a further 2 h at 90 °C. After cooling the mixture to rt the mixture was extracted with EtOAc (2 × 250 mL), was washed with aq NaHCO₃ (150 mL) and brine (150 mL), dried (MgSO₄), filtered and concentrated under reduced pressure. The crude product was flushed through a silica gel plug, eluting with petrol-EtOAc (3:2) to give crude nitrile B (0.8 g, 74%) as an amorphous solid. To a solution of crude nitrile B (567 mg, 3.06 mmol) in dry THF (12 mL) was added NaBH₄ (579 mg, 15.3 mmol). The mixture was heated at 50 °C for 1 h. After cooling to rt the mixture was diluted with water (50 mL) and EtOAc (150 mL). The organic layer was separated, was washed with brine (50 mL), dried (MgSO₄), filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel, eluting with petrol-EtOAc (1:1), gave the amine 1 (370 mg, 75%) which crystallised on standing; m.p. 52-54 °C; ¹H NMR (400 MHz, DMSO-d₆) δ = 6.96 (1H, d, J = 8.5 Hz, CH), 6.90-6.81 (1H, m, CH), 6.78-6.68 (2H, m, 2 × CH), 6.05 (1H, br s, NH), 3.77 (2H, s, CH₂), 3.23 (3H, s, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ = 165.8, 137.1, 129.0, 123.6, 118.6, 115.1, 114.0, 47.2, 28.6.

References:

Choi, Anthony;Coldham, Iain [Tetrahedron Letters,2019,vol. 60,# 37,art. no. 151023] Location in patent:supporting information