Potassium Carbonate → HCID 67140852, compound

Participants

Reaction Conditions

Reaction Steps

4-[5-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-benzoic acid can be prepared by the following procedure. To a solution of 4-(5-bromo-pyrimidin-2-ylamino)-benzoic acid methyl ester (0.3 mmol) (from Example 3f) in DMF (1.5 mL) are added 4-methoxy boronic acid (0.3 mmol), aq K2CO3 (0.68 mmol) and Pd(PPh3)4 (0.16 mmol). The reaction mixture is evacuated twice and heated at 80° C. for 30 min. After this time the reaction mixture is diluted with a sat. aq NH4Cl and extracted with DCM (3×30 mL). The organic layer is washed with brine, dried over Na2SO4 and concentrated to afford 4-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-benzoic acid methyl ester that upon trituration with MeOH gives an orange solid (95%). MS (m/z) (M+1)+ 336.1. This solid is suspended in a 3:2:1=THF:MeOH:H2O solution (3 mL) and 6N LiOH (0.15 mL) added and stirred at rt for 12 h. At this point the solvent is removed and the residue is dissolved in water and extracted with DCM (3×30 mL). The mixture is adjusted to pH ˜2 and extracted with a 3:1=DCM:IPA mixture (5×30 mL). The organic layer is washed with brine, dried over Na2SO4 and concentrated to afford 4-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-benzoic acid as an orange powder (100%) which is used without further purification. 1HNMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.87 (s, 2H), 7.95-7.87 (m, 4H), 7.71 (d, J=8.0 Hz, 2H), 7.06 (d, J=8.0 Hz, 2H), 3.81 (s, 3H). MS (m/z) (M+1)+ 322.1.

Provenance & Evidence