4-Aminopyrimidine → HCID 86649267, compound

HRID 1943416Notes

Reaction equation

HRID 1943416 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.[Cl:8][C:9]1[CH:10]=[C:11]([Cl:21])[C:12]2[N:13]([C:15]([C:18](Cl)=[O:19])=[CH:16][N:17]=2)[N:14]=1.[Br:22][C:23]1[C:24]2[N:25]([C:30]([C:33](Cl)=[O:34])=[CH:31][N:32]=2)[N:26]=[C:27]([Cl:29])[CH:28]=1>C(Cl)Cl>[Cl:8][C:9]1[CH:10]=[C:11]([Cl:21])[C:12]2[N:13]([C:15]([C:18]([NH:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)=[O:19])=[CH:16][N:17]=2)[N:14]=1.[Br:22][C:23]1[C:24]2[N:25]([C:30]([C:33]([NH:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)=[O:34])=[CH:31][N:32]=2)[N:26]=[C:27]([Cl:29])[CH:28]=1

Participants

6

Reactant 3

HCID 689584-AminopyrimidineHCID 59624647HCID 59624647, compoundHCID 59624767HCID 59624767, compound

Product 2

HCID 86649266HCID 86649266, compoundHCID 86649267HCID 86649267, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Pyrimidin-4-amine (251 mg, 2.64 mmol) was added to a ˜1:1 mixture of 6,8-dichloroimidazo[1,2-b]pyridazine-3-carbonyl chloride and 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carbonyl chloride 14A (600 mg, 2.396 mmol) and TEA (0.334 mL, 2.396 mmol) in DCM (6 mL), and the reaction mixture was stirred at room temperature for 14 hrs. The reaction mixture was filtered via Buchner funnel The solid was washed with water, and dried under high vacuum to isolate 6,8-dichloro-N-(pyrimidin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(pyrimidin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide as a brown yellow solid (726 mg, 98%), which was taken to next step without further purification. N-(4-methoxybenzyl)cyclopropanamine (381 mg, 2.148 mmol) was added to ˜1:1 mixture of 6,8-dichloro-N-(pyrimidin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(pyrimidin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (467 mg, 1.432 mmol) and DIEA (0.500 mL, 2.86 mmol) in DMF (10 mL). The reaction mixture was heated at 80° C. for 1.5 hrs. Water (20 mL) was added to the reaction mixture, and the solid was collected via Buchner filtration (with methanol wash) to isolate the title compound 6-chloro-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 14A (519 mg, 78%) as a light yellow powder. 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=2.107 (M+H=450.22).

Workup

  1. filtrationThe reaction mixture was filtered via Buchner funnel The solid
  2. washwas washed with water
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-d5bff39a82a24174be74c468f3e81e97
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

Loading…