반응 #85401

반응 방정식

hydrochloric acid

3,5-dimethyl-1,2-benzenediamine-2HCl

4-methyl-2-((3-(1-methylpiperidin-4-yl)propyl)amino)pyrimidine-5-carbaldehyde

sodium metabisulfite

potassium carbonate

→

[5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine

용매

water

water

반응 조건

후처리

1. 1
   workup.ADDITIONhalf of the volume (˜30 L) was then added, via a metering pump, to a stirring 50 L glass reactor system
2. 2
   기타resulting in the formation of a precipitate
3. 3
   기타The clear supernatant (˜20 L) was removed from the top of the 50 L reactor system
4. 4
   기타purified water (˜20 kg)
5. 5
   workup.ADDITIONwas added
6. 6
   workup.STIRRINGThe resultant mixture was stirred for 10 min
7. 7
   여과filtered
8. 8
   세척washed with water (13 kg)
9. 9
   기타dried at 35-40° C. under vacuum

실험 절차

In a 100 L glass-lined reactor, sodium metabisulfite (Na2S2O5) (1.96 kg, 9.79 mol) was dissolved in purified water (54.63 kg), followed by the addition of 3,5-dimethyl-1,2-benzenediamine-2HCl (2.07 kg, 9.86 mol) and the resultant mixture stirred at about 20-25° C. to effect solution. Next, concentrated hydrochloric acid (1.65 kg, 16.79 mol) was added, followed by addition of 4-methyl-2-((3-(1-methylpiperidin-4-yl)propyl)amino)pyrimidine-5-carbaldehyde, prepared as in STEP B above (2.74 kg, 9.79 mol) and the resultant mixture stirred at about 23-27° C. to effect solution. The resultant mixture was heated to about 57-62° C. and monitored for completion by HPLC. The reaction mixture was cooled to about 20-25° C. and then half of the volume (˜30 L) was then added, via a metering pump, to a stirring 50 L glass reactor system containing a solution of potassium carbonate (3.9 kg, 28.2 mol) dissolved in purified water (15 kg), resulting in the formation of a precipitate. The precipitated product was stirred for ˜1 h and then allowed to settle. The clear supernatant (˜20 L) was removed from the top of the 50 L reactor system and purified water (˜20 kg) was added. The resultant mixture was stirred for 10 min, filtered, washed with water (13 kg) and dried at 35-40° C. under vacuum to yield solid [5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine, compound 2. MS: [M+H]+=393, 1H NMR (600 MHz, Methanol-d6) δ, 1.38-1.43 (m, 2H), 1.43-1.52 (m, 2H), 1.53-1.61 (br m, 1H), 1.64-1.71 (m, 2H), 1.90-1.96 (br m, 2H), 2.42 (s, 3H), 2.53 (s, 3H), 2.54 (s, 3H), 2.74 (s, 3H), 2.78-2.86 (br m, 2H), 3.15-3.36 (m, 2H), 3.36-3.47 (m, 2H) 4.35 (s, 1H), 6.90 (s, 1H), 7.20 (s, 1H), 8.44 (br s, 1H).

출처