Sodium Bicarbonate → 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-N-(2,4-dimethoxybenzyl)pyridazin-3-amine

HRID 1925138Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[N:15]=[N:16][C:17](Cl)=[CH:18][CH:19]=3)([F:13])[F:12])=[N:9][N:10]=2)[CH:7]=1.[CH3:21][O:22][C:23]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:24]=1[CH2:31][NH2:32].C([O-])(O)=O.[Na+]>CC(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:13])([F:12])[C:14]3[N:15]=[N:16][C:17]([NH:32][CH2:31][C:24]4[CH:25]=[CH:26][C:27]([O:29][CH3:30])=[CH:28][C:23]=4[O:22][CH3:21])=[CH:18][CH:19]=3)=[N:9][N:10]=2)[CH:7]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A reaction mixture of 6-bromo-3-((6-chloropyridazin-3-yl)difluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (0.5 g, 1.387 mmol), (2,4-dimethoxyphenyl)methanamine (0.696 g, 4.16 mmol) and NaHCO3 (0.58 g, 7.0 mmol) in IPA (10 mL) was heated at 140° C. in a microwave for 1 hr. The solvent was removed via rotary evaporation and the resulting residue was reconstituted in EtOAc. The organic solution was washed with water, separated and passed through a short silica plug to provide the title compound, 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)-N-(2,4-dimethoxybenzyl)pyridazin-3-amine 45G (0.6 g, 1.22 mmol, 88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.71-3.76 (s, 3 H) 3.79 (s, 3 H) 3.85-3.89 (m, 2 H) 6.46 (dd, J=8.34, 2.53 Hz, 1 H) 6.57 (d, J=2.27 Hz, 1 H) 6.61-6.66 (m, 1 H) 7.08 (d, J=9.35 Hz, 1 H) 7.14 (d, J=8.34 Hz, 1 H) 7.81 (d, J=9.35 Hz, 1 H) 7.99 (dd, J=9.60, 1.01 Hz, 1 H) 8.70 (s, 1 H). ESI-MS:m/z 491.1 (M+H)+.

Workup

customThe solvent was removed via rotary evaporation
washThe organic solution was washed with water
customseparated

Sources & evidence

ORD record: ord-a179b3d340c04072a1bd495bcf69cbf9
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178534B2

Reaction notes

Loading…