Sodium hydride → 2-N-Methyl-2-N-phenyl-6-(5-{6-[(2,2,2-trifluoroethoxy)methyl]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

HRID 341432Notes

Reaction equation

HRID 341432 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([C:16]2[N:20]=[C:19]([C:21]3[CH:22]=[CH:23][C:24]([CH2:27][OH:28])=[N:25][CH:26]=3)[O:18][N:17]=2)[N:3]=1.[F:29][C:30]([F:41])([F:40])[CH2:31]OS(C(F)(F)F)(=O)=O.[H-].[Na+]>C1COCC1>[CH3:15][N:8]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:6]1[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([C:16]2[N:20]=[C:19]([C:21]3[CH:26]=[N:25][C:24]([CH2:27][O:28][CH2:31][C:30]([F:41])([F:40])[F:29])=[CH:23][CH:22]=3)[O:18][N:17]=2)[N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×HCID 66802820[5-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl]-1,2,4-oxadiazol-5-yl)pyridin-2-yl}methanol

Product 1

HCID 668027132-N-Methyl-2-N-phenyl-6-(5-{6-[(2,2,2-trifluoroethoxy)methyl]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [5-(3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-2-yl]methanol (Example 295, 30 mg, 79 μmol) in anhydrous THF (10 mL) was added trifluoromethanesulfonic acid 2,2,2-trifluoro-ethyl ester (56 mg, 239 μmol). The solution was cooled to 0 C and sodium hydride (60% dispersion in mineral oil, 7 mg, 159 μmol) was added under an inert atmosphere and the mixture was stirred at room temperature for 24 h. The reaction mixture was then re-treated with trifluoromethanesulfonic acid 2,2,2-trifluoro-ethyl ester (56 mg, 239 μmol) and sodium hydride (60% dispersion in mineral oil, 7 mg, 159 μmol) and stirred for an additional 48 h at room temperature. The reaction mixture was quenched with water (20 mL) and extracted into EtOAc (3×25 mL). Combined organics were dried over magnesium sulfate and evaporated to dryness. The crude product was purified by silica chromatography (3% MeOH in DCM) and then re-purified by preparative HPLC-MS (Method B) to afford the title compound as an off white solid (5.6 mg, 15%).

Workup

  1. additionwas added under an inert atmosphere
  2. stirringstirred for an additional 48 h at room temperature
  3. customThe reaction mixture was quenched with water (20 mL)
  4. extractionextracted into EtOAc (3×25 mL)
  5. dry with materialCombined organics were dried over magnesium sulfate
  6. customevaporated to dryness
  7. customThe crude product was purified by silica chromatography (3% MeOH in DCM)
  8. customre-purified by preparative HPLC-MS (Method B)

Sources & evidence

ORD record
ord-543da1d1bcc342fcb028275439db4624
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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