Diisopropylethylamine → HCID 71576987, compound

Participants

Reaction Steps

A mixture of 2-fluoro-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzoic acid (0.1 g, 0.28 mmol), HATU (127 mg, 0.33 mmol) and DIPEA (60 uL, 6.33 mmol) in DMF (2 mL) was stirred at room temperature for 5 min. N-Hydroxyacetimidamide (25 mg, 0.33 mmol) was added and the mixture was stirred at room temperature for 30 min followed by 100° C. for 18 h. Additional HATU (127 mg, 0.33 mmol), DIPEA (60 uL, 6.33 mmol) and N-hydroxyacetimidamide (25 mg, 0.33 mmol) were added and the reaction was heated at 100° C. for a further 8 h. The mixture was cooled and diluted with ethyl acetate (10 mL). The organic layer was washed with saturated aqueous NaHCO3 (2×5 mL) and the combined aqueous washes were extracted with further ethyl acetate (2×10 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) afforded N2-(5-fluoro-2-methoxy-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine as a white solid (16 mg, 15%). LCMS (10 cm_ESCI_Formic_MeCN): [MH+]=399 at 4.51 min. 1H NMR (400 MHz, CDCl3): δ 8.67 (d, J=13, 1H); 8.23 (s, 1H); 8.01 (s, 1H); 7.48 (d, J=6.1, 1H); 5.33 (s, 1H); 4.00 (s, 3H); 3.16 (d, J=4.7, 3H); 2.51-2.44 (m, 3H).

Provenance & Evidence