Diisopropylethylamine → HCID 45254394, compound

Participants

Reaction Steps

To a solution of 1-(4-((3-aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate C) (50 mg, 0.10 mmol) and DIPEA (33.5 μl, 0.19 mmol) in anhydrous DCM (1.0 mL) and anhydrous DMF (0.1 mL) was added methoxyacetyl chloride (10 μl, 0.11 mmol). The reaction mixture was stirred for 12 hr at RT. LC-MS indicated 50% conversion to the desired product. Methoxyacetyl chloride (10 μl, 0.11 mmol) was added and the reaction mixture was stirred at RT for a further 5 hr; LC-MS indicated the reaction was nearing completion. A further portion of methoxyacetyl chloride (8 μl, 0.09 mmol) was added, and after 2 hr, LC-MS indicated the reaction had reached completion. 1% NH3 In MeOH (10 mL) was added and the reaction mixture was stirred for 20 min at RT. The solvents were removed in vacuo to afford a purple oily solid. This was dissolved in MeOH (2.0 mL) and 3 drops of AcOH were added. The solution was subjected to SCX capture and release, eluting the product with 1% NH3 in MeOH. The solvent was removed in vacuo and the residue was triturated with diethyl ether (10 mL) to afford N-(4-((4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-3-yl)-2-methoxyacetamide (Example 16) as a light purple solid (24 mg, 41%) m/z 593 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9 H, s), 2.39 (3 H, s), 3.31 (3 H, s (obscured by DHO peak)), 4.06 (2H, s), 5.34 (2H, s), 6.35 (1H, s), 6.96 (1H, d), 7.35 (2H, d), 7.43 (2H, d), 7.64-7.54 (4H, m), 7.93 (1H, d), 8.29 (1H, dd), 8.45 (1H, d), 8.58 (1H, s), 8.70 (1H, s), 8.79 (1H, s), 9.76 (1H, s).

Provenance & Evidence