Dimethylformamide → HCID 23120475, compound

Participants

Reaction Conditions

Reaction Steps

2-[(2-bromo-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-benzamide (700 mg, 1.6 mmol) was suspended in dioxane (26 mL) and treated consecutively with DMF (7 mL), Pd2dba3 (32 mg, 0.03 mmol), Xantphos (61 mg, 0.1 mmol), cesium carbonate (632 mg, 1.9 mmol) and 1,4-dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid amide (930 mg, 5 mmol). The reaction mixture was placed under a nitrogen atmosphere and heated for 4 hours at 110° C. (bath temperature). On cooling the reaction was partitioned between EtOAc and brine. The organic phase was dried, filtered and concentrated in vacuo. The residue was purified by chromatography on Isolute® Flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 10:1) to give 1,4-dioxa-8-aza-spiro[4.5]decan-8-carboxylic acid(4-{[2-(2-methyl-2H-indazol-6-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide (574 mg, 66%) as a solid; 1H-NMR (300 MHz, d6-DMSO) 10.20 (1H, s), 9.25 (1H, s), 8.32 (1H, s), 8.21 (1H, d), 8.17 (1H, s), 8.01 (1H, t), 7.87 (1H, s), 7.75-7.80 (1H, m), 7.70 (1H, d), 7.30-7.40 (2H, m), 6.99-7.01 (1H, m), 6.73 (1H, t), 6.60 (1H, d), 4.50 (2H, d), 4.20 (3H, s), 3.97 (4H, s), 3.54-3.59 (4H, m), 1.53-1.58 (4H, m); m/z (ES+) 542 [M+H]+.

Provenance & Evidence