3-Amino-1,2-propanediol → HCID 58851498, compound

Participants

Reaction Steps

Using the same method as for Example 184, a solution of methyl 6-(3-t-butyl-5-(3-(3-(pyridin-3-yloxy)phenyl)ureido)-1H-pyrazol-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (0.017 g, 0.026 mmol, available in Example 179) in 3N HCl in MeOH (2 mL) was stirred at RT overnight. The solvent was evaporated and the residue was dissolved in MeOH (0.5 mL). 3-Amino-1,2-dihydroxypropane (0.200 g, 2.20 mmol) was added and the solution was kept at RT overnight. The mixture was directly loaded on to a reverse phase column and purified to yield 1-(1-(3-((2,3-dihydroxypropyl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-3-t-butyl-1H-pyrazol-5-yl)-3-(3-(pyridin-3-yloxy)phenyl)urea (16 mg, 97% yield) as a yellow solid. 1H-NMR (MeOH-d4): δ 8.66 (s, 1H), 8.60 (d, 1H, J=−5.6 Hz), 8.23-8.20 (m, 1H), 8.05 (dd, 1H, J=8.8, 5.6 Hz), 7.57 (t, 1H, J=2.0 Hz), 7.52-7.40 (m, 4H), 7.23 (d, 1H, J=8.4 Hz), 6.89 (dd, 1H, J=7.6, 1.6 Hz), 6.54 (s, 1H), 4.56 (d, 1H, J=16.8 Hz), 4.51 (d, 1H, J=16.8 Hz), 4.29 (dd, 1H, J=12.0, 4.4 Hz), 3.78-3.72 (m, 1H), 3.54-3.45 (m, 5H), 1.36 (s, 9H), one proton is buried under the MeOH peak, urea, amide, amine and hydroxy protons not visible. MS expected 600.3 found 600.2

Provenance & Evidence