4-Methylmorpholine → HCID 58346747, compound

Participants

Reaction Steps

To DMF (3 mL) were sequentially added [6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-2-yl]acetic acid (80 mg, 0.15 mmol), 3(R)-(−)-3(Dimethylamino)pyrrolidine (23 mg, 0.20 mmol), (3-Dimethylamino-propyl)-ethyl-carbodiimide (50 mg, 0.26 mmol), 4-methylmorpholine (0.03 ml, 0.29 mmol), and 1-Hydroxybenzotriazole (39 mg, 0.29 mmol). The mixture was stirred at rt for 14 h after which time the reaction mixture was concentrated in vacuo. The residue was diluted with water and extracted with EtOAc. The combined organic layers were concentrated in vacuo and purified by prep HPLC. The combined fractions were treated with saturated Na2CO3 and dried to afford free base product (35 mg, 42%) as a white solid. 1H-NMR (CD2Cl2) δ 8.38 (s, 1H), 7.81 (d, 1H), 7.53 (s, 1H), 7.45 (dd, 1H), 7.38 (dd, 1H), 7.28-7.22 (m, 2H), 6.97-7.08 (m, 3H), 5.15 (s, 2H), 4.84 (s, 2H), 3.64-3.80 (m, 2H), 3.15-3.53 (m, 3H), 3.07 (t, 2H), 2.61-2.81 (m, 1), 2.25 (s, 3H), 2.23 (s, 3H), 1.69-2.20 (m, 3H); LCMS RT=3.80 min, [M+H]+=632.2

Provenance & Evidence