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

HRID 341433Notes

Reaction equation

HRID 341433 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]O)=[N:25][CH:26]=3)[O:18][N:17]=2)[N:3]=1.CS(Cl)(=O)=O.[CH2:34]([N:36](CC)[CH2:37][CH3:38])[CH3:35].N1CCCC1>C(Cl)Cl>[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][N:36]4[CH2:37][CH2:38][CH2:35][CH2:34]4)=[CH:23][CH:22]=3)[O:18][N:17]=2)[N:5]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 31268PyrrolidineHCID 31297Methanesulfonyl chlorideHCID 66802820[5-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl]-1,2,4-oxadiazol-5-yl)pyridin-2-yl}methanol2×

Product 1

HCID 668033062-N-Methyl-2-N-phenyl-6-{5-[6-(pyrrolidin-1-ylmethyl)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamineYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (Intermediate 125, 50 mg, 132 μmol) in DCM (10 mL) was added methanesulfonyl chloride (11 μL, 139 μmol) and triethylamine (20 μL, 145 μmol). The reaction mixture was stirred for 90 min at room temperature under an inert atmosphere and then evaporated to dryness. The resulting solid was dissolved in DCM (10 mL), pyrrolidine (24 μL, 333 μmol) and triethylamine (46 μL, 333 μmol) and stirred for a further 3 h at room temperature. Incomplete reaction was observed so the reaction was heated at 35 C for a further 16 h. The reaction mixture was then washed with water (3×25 mL) and combined organics were dried over magnesium sulfate and evaporated to dryness. The resulting crude product was purified by silica chromatography (5% MeOH in DCM) to afford the title compound as a beige solid (25 mg, 45%).

Workup

  1. customevaporated to dryness
  2. dissolutionThe resulting solid was dissolved in DCM (10 mL)
  3. customIncomplete reaction
  4. temperaturewas heated at 35 C for a further 16 h
  5. washThe reaction mixture was then washed with water (3×25 mL)
  6. dry with materialcombined organics were dried over magnesium sulfate
  7. customevaporated to dryness
  8. customThe resulting crude product was purified by silica chromatography (5% MeOH in DCM)

Sources & evidence

ORD record
ord-6c5fd0dd7d8f4c189f3fcaea13aff489
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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