Pyrrolidine → 2-N-Methyl-2-N-phenyl-6-(5-{5-[1-(pyrrolidin-1-yl)ethyl]pyridin-2-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

HRID 341434Notes

Reaction equation

HRID 341434 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[N:26]=[CH:25][C:24]([C:27](=O)[CH3:28])=[CH:23][CH:22]=3)[O:18][N:17]=2)[N:3]=1.[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.[BH4-].[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[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:22]=[CH:23][C:24]([CH:27]([N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)[CH3:28])=[CH:25][N:26]=3)[O:18][N:17]=2)[N:5]=1

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 668026271-[6-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-3-yl]ethan-1-one

Product 1

HCID 668034252-N-Methyl-2-N-phenyl-6-(5-{5-[1-(pyrrolidin-1-yl)ethyl]pyridin-2-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamineYield 12%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[6-(3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-3-yl]ethan-1-one (prepared in an analogous manner to Example 296, 100 mg, 257 μmol) and pyrrolidine (53 μL, 643 μmol) in anhydrous THF (5 mL) at 0 C under nitrogen was added titanium isopropoxide (183 mg, 643 μmol) drop-wise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was then cooled to 0 C and sodium borohydride (29 mg, 771 μmol) was added. The reaction mixture was stirred at room temperature for 3 h and then was quenched with water (10 mL) and extracted into EtOAc (3×25 mL). Combined organics were dried over magnesium sulfate, evaporated and the crude product was purified by silica chromatography (2% MeOH in DCM) to afford the title compound as a beige solid (13 mg, 12%).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at room temperature for 3 h
  3. customwas quenched with water (10 mL)
  4. extractionextracted into EtOAc (3×25 mL)
  5. dry with materialCombined organics were dried over magnesium sulfate
  6. customevaporated
  7. customthe crude product was purified by silica chromatography (2% MeOH in DCM)

Sources & evidence

ORD record
ord-372122a568794e2b90f2a98195bd2493
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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