Reacción #1591150

Ecuación de reacción

2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethan-1-ol

2-chloro-1-(pyrrolidin-1-yl)ethan-1-one

potassium carbonate

→

2-[(4-[[(3R)-3-(2-hydroxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)(methyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one

Rendimiento 82.0%

Disolventes

DMF

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with brine
2. 2
   Secadodried over anhydrous sodium sulfate
3. 3
   Concentraciónconcentrated under vacuum

Procedimiento

To a solution of 2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethan-1-ol (120 mg, 0.35 mmol, 1.00 equiv) in distilled DMF (5 mL) was added 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (75 mg, 0.51 mmol, 1.50 equiv) and potassium carbonate (26 mg, 0.19 mmol, 2.00 equiv) at room temperature. The resulting solution was stirred overnight at room temperature. The reaction mixture was diluted with DCM (100 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with methanol/DCM (1:10) to afford the desired 2-[(4-[[(3R)-3-(2-hydroxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)(methyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one (130 mg, 82%) as a white solid. MS (ES): m/z 459 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 8.47 (1H, s), 5.32-5.20 (1H, m), 3.66 (2H, t), 3.58 (2H, t), 3.50-3.41 (3H, m), 3.37 (2H, s), 3.15-3.05 (1H, m), 3.00-2.92 (1H, m), 2.75-2.60 (2H, m), 2.37 (3H, s), 2.33-2.15 (4H, m), 2.03-1.88 (6H, m), 1.71-1.54 (4H, m).

Fuente