4-Amino-2-methylpyridine → 6-chloro-8-((4-methoxybenzyl)(phenyl)amino)-N-(2-methylpyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943498Notes

Reaction equation

HRID 1943498 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:14]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:5]2[N:6]([C:8]([C:11](O)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:30][C:31]1[CH:36]=[C:35]([NH2:37])[CH:34]=[CH:33][N:32]=1>O=S(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([N:14]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:5]2[N:6]([C:8]([C:11]([NH:37][C:35]3[CH:34]=[CH:33][N:32]=[C:31]([CH3:30])[CH:36]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1

Participants

4

Reactant 2

HCID 7286704-Amino-2-methylpyridineHCID 596248836-Chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acid

Product 1

HCID 596246286-chloro-8-((4-methoxybenzyl)(phenyl)amino)-N-(2-methylpyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideYield 55.2%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

6-Chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acid (150 mg, 0.37 mmol) in SOCl2 (2 mL) was heated at 60° C. for 1 hour. The reaction mixture was concentrated, dried under reduced pressure and dissolved in DCM (3 mL). 2-Methylpyridin-4-amine (45 mg, 0.41 mmol), and TEA (0.16 mL, 1.11 mmol) were added and the reaction mixture was stirred at room temperature for 12 hours, concentrated and then purified by silica gel chromatography (5% MeOH in DCM) to obtain 6-chloro-8-((4-methoxybenzyl)(phenyl)amino)-N-(2-methylpyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (102 mg, 55% yield) as a yellow solid. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA). Rt=3.263 minutes. [M+H]=499.06.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customdried under reduced pressure
  3. dissolutiondissolved in DCM (3 mL)
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography (5% MeOH in DCM)

Sources & evidence

ORD record
ord-e7c76ce73f8743a69e35bb53641aa026
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

Loading…