4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline → N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine

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Reaction Steps

2-chloro-7-(4-fluorophenyl)-N-methyl-5,7-dihydrofuro[3,4-d]pyrimidin-4-amine (Preparation Ma) (149 mg, 0.533 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (Preparation A) (119 mg, 0.533 mmol) were combined and purified as per Example 75 to give the racemate N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine which was separated by multiple chiral SFC injections (OJ-H 30×250 mm, 5 μM, 35% MeOH (0.1% DEA)/CO2) to give N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine (second to elute, enantiomer B) (22.1 mg, 0.047 mmol, 8.89% yield) as a slightly yellow scrapable foam. LC-MS (M+H)+=467.0. 1H NMR (500 MHz, MeOD) δ ppm 7.92 (1H, d, J=2.14 Hz), 7.68 (1H, d, J=1.53 Hz), 7.39 (2H, dd, J=8.70, 5.34 Hz), 7.22 (1H, d, J=1.53 Hz), 7.15 (1H, d, J=8.55 Hz), 7.04-7.11 (3H, m), 5.79 (1H, br. s.), 5.12 (1H, dd, J=10.99, 3.36 Hz), 4.99 (1H, d, J=10.99 Hz), 3.70 (3H, s), 3.05 (3H, s). The absolute stereochemistry of Example 79B was not determined.

Provenance & Evidence