1-Hydroxybenzotriazole → HCID 11988445, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(3-chloro-4-cyano-2-methylphenyl)proline (0.200 g, 0.756 mmol), TBTU (0.364 g, 1.136 mmol), diisopropylethylamine (0.458 g, 3.78 mmol) and N-hydroxybenzotriazole (0.023 g, 0.150 mmol) in DMF add N-hydroxyacetamidine (0.084 g, 1.136 mmol). Stir the solution at 21° C. for 18 h. then heat the reaction at 100° C. in a microwave for 1 h. Partition the reaction between ethyl acetate and 2N aqueous hydrochloric acid. Extract the organic phase with 2N aqueous sodium hydroxide and brine, dry over magnesium sulphate, filter and remove the solvent under reduced pressure. Purify the resulting residue by reverse phase HPLC (Princeton SPHER C-18 column, gradient of 80:20 to 5:95 [water:acetonitrile], with 0.1% acetic acid modifier)) to yield the title compound. (0.81 g, 35%) mass spectrum (m/e): 303.1 (M+Na)); 1H NMR (400 MHz, CDCl3): δ 7.35 (d, 1H), 6.99 (d, 1H), 5.11 (t, 1H), 3.88 (m, 1H), 3.16 (m, 1H), 2.56 (m, 1H), 2.39 (s, 3H), 2.31 (s, 3H), 2.30-2.15 (m. 3H), 2.06 (m, 1H).

Provenance & Evidence