HCID 59764747, compound → HCID 59764658, compound

Participants

Reaction Steps

2-(6,7-dichloroquinazolin-4-ylamino)-1-(3-(4-(4-fluorophenyl)-4-hydroxy-3-methylpiperidin-1-yl)pyrrolidin-1-yl)ethanone was prepared as a mixture of 4 isomers from (3S,4R)-4-(4-fluorophenyl)-3-methylpiperidin-4-ol (prepared via general procedure O, AA) and 1-(2-(6,7-Dichloroquinazolin-4-ylamino)acetyl)pyrrolidin-3-one (Preparation #32) according to general procedure E then purified via chiral preparative NP-HPLC (isocratic 2.5% methanol:2.5% ethanol:95% heptane:0.1% diethylamine modifier at 16 mL/min, room temperature; UV detection monitored at 265 nm; Daicel AD-H column, 20×250 mm, 5 um particle) to yield two products. Product A eluted at Rt 7.5-11 min. Product B eluted at Rt 11-15 min. Product A has a positive optical rotation and product B has a negative optical rotation. Product A was further separated via chiral preparative NP-HPLC (isocratic 10% methanol:10% ethanol:80% heptane:0.1% diethylamine modifier at 14 mL/min, room temperature; UV detection monitored at 265 nm; Daicel OD-H column, 20×250 mm, 5 um particle) to yield two isomers. Isomer 1 eluted at Rt 14-16.3 min. Isomer 2 eluted at Rt 16.3-19 min. Both isomers have positive optical rotation. The absolute stereochemistry of the isomers was not assigned. Isomers 1 & 2: RP-HPLC (Table 1, Method a) Rt 1.99 min; m/z: (M+H)+ 532. Product B was further separated via chiral preparative NP-HPLC (isocratic 10% methanol:10% ethanol:80% heptane:0.1% diethylamine modifier at 14 mL/min, room temperature; UV detection monitored at 265 nm; Daicel OD-H column, 20×250 mm, 5 um particle) to yield two isomers. Isomer 3 eluted at Rt 13.3-16 min. Isomer 4 eluted at Rt 16.3-19 min. Both isomers have negative optical rotation. The absolute stereochemistry of the isomers was not assigned. Isomers 3 & 4: RP-HPLC (Table 1, Method a) Rt 1.92 min; m/z: (M+H)+ 532.

Provenance & Evidence