Methyl 5-(3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridine-2-carboxylate → 1-[5-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-2-yl]ethan-1-one

HRID 341436Notes

Reaction equation

HRID 341436 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]([C:27]([O:29]C)=O)=[N:25][CH:26]=3)[O:18][N:17]=2)[N:3]=1.[CH3:31][Mg]Br>C1COCC1>[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]([C:27](=[O:29])[CH3:31])=[N:25][CH:26]=3)[O:18][N:17]=2)[N:3]=1

Participants

4

Reactant 2

HCID 66803428Methyl 5-(3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridine-2-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 668028961-[5-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-2-yl]ethan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-(3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridine-2-carboxylate (prepared in an analogous manner to Example 279, 1.00 g, 2.47 mmol) in anhydrous THF (30 mL) at −78 C was added methyl magnesium bromide (3M sol. in ether, 907 μL, 2.72 mmol) drop wise under an inert atmosphere. The resulting solution was stirred at −78 C for 1 h and then allowed to warm to room temperature where upon stirring was continued for a further 1 h. The reaction mixture was cooled again and quenched with acetone (1 mL) and a 10% citric acid aq. solution (5 mL). The reaction mixture was extracted with EtOAc (3×50 mL) and the resultant organics washed with brine (25 mL), dried over magnesium sulfate and evaporated to dryness. 50 milligrams of the resulting crude material was purified by preparative HPLC-MS (Method C) to afford the title compound as an off white solid (21 mg).

Workup

  1. stirringupon stirring
  2. waitwas continued for a further 1 h
  3. temperatureThe reaction mixture was cooled again
  4. customquenched with acetone (1 mL)
  5. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
  6. washthe resultant organics washed with brine (25 mL)
  7. dry with materialdried over magnesium sulfate
  8. customevaporated to dryness
  9. custom50 milligrams of the resulting crude material was purified by preparative HPLC-MS (Method C)

Sources & evidence

ORD record
ord-4d60f0d0fb75406993584671f1c72501
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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