Formic Acid → 4-Methyl-2-((3-(1-methylpiperidin-4-yl)propyl)amino)pyrimidine-5-carbaldehyde

Temperature

12.5 °C

A vessel at room temperature was charged with formic acid (800 mL) and 4-methyl-2-(3-(1-methylpiperidin-4-yl)propylamino)pyrimidine-5-carbonitrile (100 g) and the resulting mixture stirred to yield a clear solution, then cooled to 10-15° C. Water (200 mL) was added and the resulting mixture cooled to −2 to 0° C. To the resulting mixture was then added RANEY® nickel (160 g) maintaining the temperature at −2 to 0° C. and then stirred at this temperature for 2-3 hours. The resulting mixture was then filtered to remove the RANEY® nickel and the filtercake washed with water (100 mL), The filtrate was cooled to 0-5° C. and then slowly treated with 50% sodium carbonate solution in water (3.0 L) to adjust the pH of the solution to pH˜10. Toluene (400 mL) was added and the resulting mixture stirred at room temperature for about 30 minutes, then allowed to settle for about 1 hour. The resulting layers were separated and the aqueous layer washed with toluene (400 mL×2). The combined toluene layer and washed were distilled at 55-60° C. to remove the toluene, to yield the title compound as an oily residue.

1. customto yield a clear solution
2. temperaturethe resulting mixture cooled to −2 to 0° C
3. stirringstirred at this temperature for 2-3 hours
4. filtrationThe resulting mixture was then filtered
5. customto remove the RANEY® nickel
6. washthe filtercake washed with water (100 mL)
7. temperatureThe filtrate was cooled to 0-5° C.
8. additionslowly treated with 50% sodium carbonate solution in water (3.0 L)
9. additionToluene (400 mL) was added
10. stirringthe resulting mixture stirred at room temperature for about 30 minutes
11. customThe resulting layers were separated
12. washthe aqueous layer washed with toluene (400 mL×2)
13. washThe combined toluene layer and washed
14. distillationwere distilled at 55-60° C.
15. customto remove the toluene

ORD record

ord-a02ce4b3685d4c84836e229216202998

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835633B2