3-Methoxypropylamine → 4-[({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}amino)sulfonyl]-N-(3-methoxypropyl)benzamide

Participants

Reaction Steps

4-[({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}amino)sulfonyl]benzoic acid (100 mg; 0.21 mmol; 1 eq.), EDC-HCl (51.87 mg; 0.27 mmol; 1.3 eq.) and HOBT (36.56 mg; 0.27 mmol; 1.3 eq.) were taken up in DMA (5 ml) then DIEA (106.88 μl; 0.62 mmol; 3 eq.) and 3-methoxypropylamine (21.23 μl; 0.21 mmol; 1 eq.) were added. The solution was stirred at rt for 3 h. The DMA was evaporated and the residue was taken up in DCM. The organic phase was washed with a saturated solution of NaHCO3 then a saturated solution of NH4Cl and brine. It was dried over MgSO4 and concentrated to near dryness. The residue obtained was taken up in ACN and refluxed. After cooling at 4° C., the precipitate was filtered off then washed with ACN to afford 76 mg (66%) of the title compound as a parent. Treatment of the parent (74 mg; 0.13 mmol; 1 eq.) with an aqueous solution of potassium hydroxide (268.30 μl; 0.5 M; 0.13 mmol; 1 eq.) affords 76 mg (96%) of the title compound as a yellow powder. 1H NMR (DMSO-d6) δ 8.77 (s, 1H), 8.49-8.45 (m, 1H), 8.08 (d, J=8.3 Hz, 2H), 7.80 (d, J=8.3 Hz, 2H), 7.41-7.38 (m, 1H), 7.31 (d, J=2.3 Hz, 2H), 7.27-7.24 (m, 1H), 7.17-7.08 (m, 2H), 6.13-6.12 (m, 1H), 3.77 (s, 6H), 3.35-3.31 (m, 2H), 3.28-3.22 (m, 2H), 3.20 (s, 3H), 1.75-1.66 (m, 2H). HPLC (max plot) 97%; Rt 4.17 min. LC/MS: (ES+): 552.4, (ES−): 550.3.

Provenance & Evidence