Hydrochloric Acid → N-[4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl]-4-(6-(dimethylamino)quinolin-4-ylamino)benzamide hydrochloride

Participants

Reaction Steps

To a solution of amide E5 (228 mg, 0.62 mmol) in 1:2 EtOH:H2O (20 mL) were sequentially added c.HCl (0.17 mL, 5.61 mmol) and 4-chloro-6-dimethylaminoquinoline (03) (140 mg, 0.68 mmol), and the resulting mixture was refluxed for ˜12 h. MS and TLC analysis (eluting with the top phase of a 5:4:1 mixture of n-BuOH:H2O:AcOH) after this time showed some starting material still present in the reaction mixture, thus more 03 (140 mg, 0.68 mmol) was added. After a further few hours refluxing, TLC showed the reaction was complete, and thus solvent was removed under reduced pressure. The residue was crystallized from MeOH:EtOAc to afford Cpd. P as an (extremely fine) amorphous yellow solid (170 mg, 51%). 1H NMR [(CD3)2SO] δ2.28 [s, 3H], 3.15 [s, 6H, ArN(CH3)2], 6.21 [br s, 1 H, ArH], 6.89 [d, J=6.71 Hz, 1 H, ArH], 7.65 [m, 5 H, ArH], 7.82 [m, 4 H, ArH & ArNH2], 7.96 [d, J=9.39 Hz, 1 H, ArH], 8.18 [d, J=8.57 Hz, 2 H, ArH], 8.35 [t, J=12.38, 6.19 Hz, 1 H, ArH], 10.44 [br s, 1 H, ArH], 10.65 [br s, 1 H, ArNHAr], 10.71 [s, 1 H, ArNHAr], 12.75 [br s, 1 H, ArC(O)NH], 14.56 [d, J=4.10 Hz, 1 H, quinolinyl N+H]. LCMS (APCI+): 506 (100%). HPLC: 97.6%.

Provenance & Evidence