1,4-Dioxane → {3-[4-Amino-6-(methyl-phenyl-amino)-[1,3,5]triazin-2-yl]-[1,2,4]oxadiazol-5-yl}-[3-(4-fluoro-phenyl)-azetidin-1-yl]-methanone

HRID 341419Notes

Reaction equation

HRID 341419 reaction equation
[CH3:1][N:2]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:3]1[N:8]=[C:7]([NH2:9])[N:6]=[C:5]([C:10]2[N:14]=[C:13]([C:15](Cl)(Cl)Cl)[O:12][N:11]=2)[N:4]=1.Cl.[F:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]2[CH2:36][NH:35][CH2:34]2)=[CH:29][CH:28]=1.[O:37]1CCOCC1>C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[NH2:9][C:7]1[N:8]=[C:3]([N:2]([CH3:1])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:4]=[C:5]([C:10]2[N:14]=[C:13]([C:15]([N:35]3[CH2:34][CH:33]([C:30]4[CH:29]=[CH:28][C:27]([F:26])=[CH:32][CH:31]=4)[CH2:36]3)=[O:37])[O:12][N:11]=2)[N:6]=1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 552509373-(4-Fluorophenyl)azetidine hydrochloride2×HCID 66802564N-methyl-N-phenyl-6-(5-trichloromethyl-[1,2,4]oxadiazol-3-yl)-[1,3,5]triazine-2,4-diamine2×

Product 1

HCID 66803024{3-[4-Amino-6-(methyl-phenyl-amino)-[1,3,5]triazin-2-yl]-[1,2,4]oxadiazol-5-yl}-[3-(4-fluoro-phenyl)-azetidin-1-yl]-methanoneYield 65%

Reagents, catalysts & solvents 1

HCID 311Citric AcidSolvent

Procedure

To N-methyl-N-phenyl-6-(5-trichloromethyl-[1,2,4]oxadiazol-3-yl)-[1,3,5]triazine-2,4-diamine (prepared in an analogous manner to Intermediate 60, 63 mg, 0.16 mmol) was added 3-(4-fluoro-phenyl)-azetidine hydrochloride (Intermediate 122, 39 mg, 0.19 mmol). Disiopropylethylamine (42 μL) and dioxane (1 mL) were added and the mixture heated at 70 C for 4 h. The mixture was diluted with 1 M citric acid to give a precipitate which was filtered. The pad was washed with a 1 M aq. solution of sodium bicarbonate (2 mL), water (2 mL) and then the solid was slurried in MeOH (2 mL) to give the title compound (48 mg, 65%).

Workup

  1. temperaturethe mixture heated at 70 C for 4 h
  2. customto give a precipitate which
  3. filtrationwas filtered
  4. washThe pad was washed with a 1 M aq. solution of sodium bicarbonate (2 mL), water (2 mL)

Sources & evidence

ORD record
ord-8c847c9c242840b7aab4337bb8fa545d
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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