Diisopropylethylamine → 6-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943433Notes

Reaction equation

HRID 1943433 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](Cl)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([Cl:20])[CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.BrC1C2N(C(C(NC3C=CN=C(Cl)C=3)=O)=CN=2)N=C(Cl)C=1.[CH3:43][O:44][C:45]1[CH:55]=[CH:54][C:48]([CH2:49][NH:50][CH:51]2[CH2:53][CH2:52]2)=[CH:47][CH:46]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:50]([CH:51]2[CH2:53][CH2:52]2)[CH2:49][C:48]2[CH:54]=[CH:55][C:45]([O:44][CH3:43])=[CH:46][CH:47]=2)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([Cl:20])[CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4721289N-((4-methoxyphenyl)methyl)cyclopropanamineHCID 596245318-Bromo-6-chloro-N-(2-chloropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideHCID 596247816,8-Dichloro-N-(2-chloropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 596248746-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamideYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A ˜1:1 mixture 6,8-dichloro-N-(2-chloropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(2-chloropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (3 g, 8.6 mmol), N-(4-methoxybenzyl)cyclopropanamine (8.16 g, 23.82 mmol) and N,N-diisopropylethylamine (3.08 g, 23.82 mmol) was suspended in DMF (100 mL) and heated at 80° C. for 1.5 hrs. The reaction mixture was concentrated and dried under reduced pressure for 16 hrs. The residue was suspended in methanol (75 mL) and an off-white solid was collected via Buchner filtration (2×25 mL methanol rinse) to isolate 6-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (10.2 g, 21.1 mmol, 89%) as a tan 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=2.21 minutes. [M+H]=483.06.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customdried under reduced pressure for 16 hrs
  3. filtrationan off-white solid was collected via Buchner filtration (2×25 mL methanol rinse)

Sources & evidence

ORD record
ord-b94e46c31e10470aa8a4efde85be44e8
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

Loading…