Diisopropylethylamine → HCID 25171612, compound

Participants

Reaction Steps

(S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-((S)-pyrrolidin-2-yl)ethanone (28 mg, 0.53 mmol; see Example 3) was slurried in acetone (0.4 mL) and treated with diisopropylethylamine (0.032 mL, 0.18 mmol), 4-dimethylaminopyridine (“DMAP”; 0.0006 g, 0.005 mmol) and 3,3,3-trifluoropropyl trifluoromethanesulfonate (0.016 g, 0.066 mmol). The reaction mixture was heated to reflux for 9 hours. Additional 3,3,3-trifluoropropyl trifluoromethanesulfonate (0.016 g, 0.066 mmol) was added and the mixture was heated at reflux for 16 hours. The reaction was concentrated using N2 (g) and chromatographed on SiO2 eluting with 2% MeOH/methylene chloride. After chromatography, the product was dissolved in ethyl acetate and washed 3 times with saturated NH4Cl, once with saturated NaHCO3, once with saturated NaCl, dried over Na2SO4 and concentrated in vacuo. The residue was concentrated from dioxane, treated with 4M HCl in dioxane (2 mL) and concentrated in vacuo. The salt was redissolved in MeOH and re-concentrated three times. The salt was dissolved in a minimal amount of MeOH and added dropwise to Et2O. The salt was filtered and washed with Et2O then dried under vacuum (12.8 mg, 39%). MS (ESI+) [M+H] 538.2/540.1. 1H NMR (CD3OD, 400 MHz) δ □8.58 (s, 1H), 7.47-7.36 (m, 4H), 5.31 (t, 1H), 4.48-3.96 (m, 3H), 3.91-3.44 (m, 7H), 2.35-2.27 (m, 1H), 2.23-2.13 (m, 1H), 2.05-1.88 (m, 2H), 1.84-1.71 (m, 1H), 1.68-1.56 (m, 1H), 1.19 (d, 3H).

Provenance & Evidence