Sodium Iodide → N-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-1,5-naphthyridin-4-amine

HRID 40195

Reaction equation

HRID 40195 reaction equation
[C:1](=O)([O-])[O-:2].[Cs+].[Cs+].[C:7]1([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([CH2:22][NH:23][C:24]4[CH:25]=[CH:26][N:27]=[C:28]5[C:33]=4[N:32]=[CH:31][C:30]([OH:34])=[CH:29]5)=[N:20][N:21]=3)[N:18]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.Cl[CH2:37][CH2:38][N:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1.[I-].[Na+]>CS(C)=O.O>[CH3:1][OH:2].[NH4+:17].[OH-:34].[C:7]1([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([CH2:22][NH:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([O:34][CH2:37][CH2:38][N:39]6[CH2:43][CH2:42][CH2:41][CH2:40]6)=[CH:31][N:32]=5)[N:27]=[CH:26][CH:25]=4)=[N:20][N:21]=3)[N:18]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 1359874788-((6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylamino)-1,5-naphthyridin-3-ol

Product 2

HCID 21894508Ammonium hydroxide methanolHCID 57691301N-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-1,5-naphthyridin-4-amineYield 22.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

In a 10 mL sealed tube under N2 were dissolved CESIUM CARBONATE (221 mg, 677 μmol), 8-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylamino)-1,5-naphthyridin-3-ol (50 mg, 135 μmol), 1-(2-chloroethyl)pyrrolidine hydrochloride (46 mg, 271 μmol) and SODIUM IODIDE (41 mg, 271 μmol) in 1 mL of DMSO then stirred and heated at 75° C. for 3 h. The reaction mixture was diluted with H2O and the aqueous phase was extracted 3× with DCM then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was purified by MPLC (ISCO) with DCM/DCM:MeOH:NH4OH (90:10:1)100:0 to 90:10 to afforded N-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-1,5-naphthyridin-4-amine (7 mg, 11% yield) as a yellow solid. MS m/z=466.2 [M+1]+. Calc'd for C26H26N8O: 467.0.

Workup

  1. customIn a 10 mL sealed tube under N2
  2. extractionthe aqueous phase was extracted 3× with DCM
  3. dry with materialthe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude mixture was purified by MPLC (ISCO) with DCM/DCM

Sources & evidence

ORD record
ord-bbfaf995e8d949f080af9e7cd0b469b2
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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