Acryloyl chloride → HCID 86677232, compound

Participants

Reaction Conditions

Reaction Steps

Acryloyl chloride (0.025 mL, 0.30 mmol) was added dropwise to N′-[4-(1H-indol-3-yl)-5-methylpyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 12, 135 mg, 0.30 mmol) and DIPEA (0.090 mL, 0.33 mmol) in CH2Cl2 (10 mL) and DMF (2 mL) at 0° C. under N2. The resulting suspension was stirred at 0° C. for 2 h. then allowed to warm to r.t. The mixture was then diluted with water (15 mL) and extracted with CH2Cl2 (40 mL). The resulting organic solution was washed with sat. Na2CO3 (20 mL) and then sat. brine (20 mL). The solution was then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-5% 7M methanolic ammonia in CH2Cl2 gave crude product. Further purification by preparative HPLC (Waters SunFire column, 5μ it silica, 19 mm diameter, 100 mm length), eluting with decreasingly polar mixtures of water (containing 0.1% formic acid) and CH3CN, followed by HPLC (Waters XBridge Prep C18 OBD column, 5μ it silica, 19 mm diameter, 100 mm length), eluting with decreasingly polar mixtures of water (containing 1% NH3) and CH3CN, gave the title compound (23 mg, 15%) as a white solid; 1H NMR: 2.26 (3H, s), 2.37 (3H, s), 2.48-2.57 (4H, m), 2.87 (4H, t), 3.84 (3H, s), 5.70 (1H, d), 6.18 (1H, dd), 6.59 (1H, dd), 6.87 (1H, s), 7.05 (1H, dd), 7.15 (1H, t), 7.44 (1H, d), 7.83 (1H, s), 7.98 (1H, d), 8.22 (1H, s), 8.34 (1H, d), 8.49 (1H, s), 8.97 (1H, s), 11.68 (1H, s); m/z: ES+ MH+ 498.60.

Provenance & Evidence