Potassium Carbonate → 6-(5-{4-[(Cyclopropylmethoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine

HRID 341425Notes

Reaction equation

HRID 341425 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][N:8]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:9]1[N:14]=[C:13]([NH2:15])[N:12]=[C:11]([C:16]2[N:20]=[C:19](C(Cl)(Cl)Cl)[O:18][N:17]=2)[N:10]=1.Cl.[CH:32]1([CH2:35][O:36][CH2:37][CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH2:34][CH2:33]1>CN(C=O)C>[CH:32]1([CH2:35][O:36][CH2:37][CH:38]2[CH2:43][CH2:42][N:41]([C:19]3[O:18][N:17]=[C:16]([C:11]4[N:10]=[C:9]([N:8]([CH3:7])[C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:14]=[C:13]([NH2:15])[N:12]=4)[N:20]=3)[CH2:40][CH2:39]2)[CH2:33][CH2:34]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 237229874-[(Cyclopropylmethoxy)methyl]piperidine 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 668028916-(5-{4-[(Cyclopropylmethoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamineYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (0.107 g, 0.776 mmol) and 2-N-methyl-2-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, 0.150 g, 0.388 mmol) were added to a solution of 4-[(cyclopropylmethoxy)methyl]piperidine hydrochloride salt (Intermediate 198, 0.160 g, 0.776 mmol) in DMF (5 mL) at room temperature. The reaction mixture was stirred at room temperature for 18 h and then evaporated under vacuum to remove the DMF. The crude residue was dissolved in EtOAc (5 mL) and washed with water (3×3 mL). The aqueous washes were combined, re-extracted with EtOAc (2×3 mL). The organic extracts were combined, dried over sodium sulfate, filtered and evaporated to provide a crude brown residue which was purified by preparative HPLC, Method B, to afford the title compound as an off-white solid (28 mg, 16%).

Workup

  1. customevaporated under vacuum
  2. customto remove the DMF
  3. dissolutionThe crude residue was dissolved in EtOAc (5 mL)
  4. washwashed with water (3×3 mL)
  5. extractionre-extracted with EtOAc (2×3 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto provide a crude brown residue which
  10. customwas purified by preparative HPLC, Method B

Sources & evidence

ORD record
ord-df5ad36596c14242b4191d1108cd4061
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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