| 73% |
In 1,4-dioxane at 80℃; for 18h; |
1; 2 Example-2: Preparation of pure Mavacamten
6-Chloro-3 -isopropyl-pyrimidine-2,4-dione (80 g) and 1 ,4-dioxane (400 mL) were charged into a 2000 mL round bottomed flask. (S)-(-)-cL-methylbenzylamine (154.2 g) was added slowly. The mixture was heated to 80 °C and stirred for 18 hours. TLC showed complete consumption of starting material. The reaction mixture was concentrated under vacuum at 80 °C and then cooled to 25 °C. Water (1600 mL) was then added, the mixture obtained was then stirred for 15 minutes, and extracted with ethyl acetate (2 x 800 mL). The organic layer was separated and washed with iN HC1 (400 mL) and brine (800 mL).The product which precipitated from the organic layer was filtered, washed with ethyl acetate (200 mL) and dried under vacuum at 40 °C. Yield: 85 g (Crop 1), Yield: 73%. Purity: 99.84% by HPLC. PXRD pattern is shown in Figure 1. |
| 69% |
In 1,4-dioxane at 90℃; |
1 Compound 1. (S)-3-isopropyl-6-((1-phenylethyl)amino)pyrimidine-2,4(1H,3H)-dione
To a solution of 6-chloro-3-isopropylpyrimidine-2,4(lH,3H)-dione (1.3, 1.0 g, 5.31 mmol) in 1,4-dioxane (20 mL) was added (S)-a-methylbenzylamine (Sigma- Aldrich, 1.43 g, 11.7 mmol, 2.2 equiv). The reaction mixture was stirred at 80 °C for 24 h. After cooling to ambient temperature, the mixture was concentrated under reduced pressure. The residual was taken up in EtOAc (70 mL) and washed with aqueous IN HC1 (2 x 50 mL) and brine (40 mL). The organic layer was dried with anhydrous Na2SC"4 and then concentrated under reduced pressure to half the original volume to yield a precipitate. Hexane (20 mL) was added and the mixture was stirred at room temperature. The resulting solid was collected by filtration, washed with hexane (20 mL), and dried to yield 1.0 g (69%) of the title compound as a white solid. LC/MS: m/z (ES+) 274 (M+H)+. 1H-NMR (400 MHz, de-DMSO): δ 9.77 (s, 1H), 7.32 (m, 4H), 7.24 (m, 1H), 6.50 (d, J= 6.8 Hz, 1H), 4.87 (m, 1H), 4.52 (m, 1H), 4.31 (d, J=6.8 Hz, 1H), 1.37 (m, 3H ), 1.24 (m, 6H). 1H NMR (400 MHz, CD3OD) δ ppm 7.39-7.20 (m, 5H), 5.01 (m, 1H), 4.48 (m, 1H), 1.49 (d, J = 6.7 Hz, 3H), 1.36 (m, 6H). |
| 69% |
In 1,4-dioxane for 24h; |
1 Compound 1. (8)-3-Isopropyl-6-((1-phenylethyl) amino) pyrimidine-2,4(1H,3H)-dione.
To a solution of 6-chloro-3-isopropylpyrimidine-2,4( 1H,3H)-dione (1.3,1.0 g, 5.31 mmol) in 1,4-dioxane (20 mL) was added (S)-ct-methylbenzylamine (Sigma-Aldrich, 1.43 g, 11.7 mmol, 2.2 equiv). The reaction mixture was stirred at 80 °C for 24 h.After cooling to ambient temperature, the mixture was concentrated under reduced pressure.The residual was taken up in EtOAc (70 mL) and washed with aqueous iN HC1 (2 x 50 mL)and brine (40 mL). The organic layer was dried with anhydrous Na2SO4 and then concentrated under reduced pressure to half the original volume to yield a precipitate. Hexane (20 mL) was added and the mixture was stirred at room temperature. The resulting solid was collected by filtration, washed with hexane (20 mL), and dried to yield 1.0 g (69%)of the title compound as a white solid. LC/MS: mlz (ES+) 274 (M+H)t ‘H-NMR (400 MHz, d6-DMSO): ö 9.77 (s, 1H), 7.32 (m, 4H), 7.24 (m, 1H), 6.50 (d, J= 6.8 Hz, 1H), 4.87 (m, 1H), 4.52 (m, 1H), 4.31 (d, J=6.8 Hz, 1H), 1.37 (m, 3H), 1.24 (m, 6H). ‘H NMR (400 MHz,CD3OD) ö ppm 7.39-7.20 (m, 5H), 5.01 (m, 1H), 4.48 (m, 1H), 1.49 (d, J = 6.7 Hz, 3H), 1.36 (m, 6H). |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
