反应详情

温度

100 °C

N-(4-Fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 129, 295 mg, 0.75 mmol), ((3S)—N,N-dimethylpyrrolidin-3-amine (103 mg, 0.90 mmol) and DIPEA (0.196 mL, 1.13 mmol) were dissolved in DMA (3 mL) and sealed into a microwave tube. The mixture was heated to 100° C. for 45 minutes in a microwave reactor, then cooled to r.t., diluted with CH3OH and absorbed onto an SCX column. The column was washed with CH3OH and then eluted with 1:1 methanolic ammonia in CH2Cl2. Fractions containing the desired product were combined and concentrated in vacuo. Purification by FCC, eluting with 2-7% methanolic ammonia in CH2Cl2 gave the title compound (235 mg, 64%) as a red solid; 1H NMR: 1.83 (1H, m), 2.17 (1H, m), 2.22 (6H, s), 2.72-2.86 (1H, m), 3.17 (2H, m), 3.26 (1H, m), 3.47 (1H, m), 3.88 (3H, s), 3.97 (3H, s), 6.58 (1H, s), 7.12 (1H, t), 7.19 (1H, d), 7.21-7.31 (1H, m), 7.52 (1H, d), 8.01 (1H, s), 8.23-8.33 (2H, m), 8.36 (1H, d), 8.58 (1H, s); m/z: ES− MH+ 488.35.

1. customsealed into a microwave tube
2. temperaturecooled to r.t.
3. customabsorbed onto an SCX column
4. washThe column was washed with CH3OH
5. washeluted with 1:1 methanolic ammonia in CH2Cl2
6. additionFractions containing the desired product
7. concentrationconcentrated in vacuo
8. customPurification by FCC
9. washeluting with 2-7% methanolic ammonia in CH2Cl2