1-methyl-3-((methylamino)methyl)-1H-pyrazole-5-carbonitrilehydrochloride
Bezeichnung:1-methyl-3-((methylamino)methyl)-1H-pyrazole-5-carbonitrilehydrochloride
CAS-Nr1643141-20-1
Englisch Name:1-methyl-3-((methylamino)methyl)-1H-pyrazole-5-carbonitrilehydrochloride
CBNumberCB03054477
SummenformelC7H11ClN4
Molgewicht186.64
MOL-Datei1643141-20-1.mol
To compound 19 (7.0 kg, 26.1 mol) in DCM (30 L) at O℃ was added triethylamine (5.85
kg, 57.8 mol). The mixture was further cooled to -6°C then trifluoroacetic anhydride (5.85 kg, 27.8
mol) added over 90 minutes [temp kept 0 to 5°C], TLC assay showed the reaction was
incomplete. Additional triethylamine (4.1 kg, 40.5 mol) and trifluoroacetic acid (4.1 kg, 19.5 mol)
10 were added over 2 hours until TLC showed complete reaction. The reaction mixture was
quenched in to water (40 L) [temp to 23°C], The layers were separated and the aqueous re-
extracted with DCM (8 L). The organic layers were sequentially washed with brine (7 L), filtered
through a pad of silica (3 kg) and eluted with DCM (10 L). The filtrate was evaporated and
chromatographed (9 kg silica, eluent 10-30% EtOAc in hexane). Product fractions were
15 evaporated and azeotroped with IPA to afford compound 20 (6.86 kg, ~94 wt%, 25.8 mol, 99%)
as an orange oil. To compound 20 (6.86 kg, ~94 wt%, 25.8 mol) in IPA (35 L) at 17°C was added 37%
hydrochloric acid (6.4 L, 77.4 mol). The mixture was heated to 35°C overnight then concentrated
20 to a moist solid and residual water azeotroped with additional IPA (8 L). The resulting moist solid
was triturated with MTBE (12 L) at 45°C for 30 minutes then cooled to 20°C and filtered, washing
with MTBE (5 L). The solids were dried under vacuum at 45°C to afford compound 21 (4.52 kg,
24.2 mol, 94%) as a white solid. 1H-NMR was consistent with desired product; mp 203-205°C;
HPLC 99.3%.