1,1'-Carbonyldiimidazole → 6-{5-[3-(Cyclopropylamino)pyridin-2-yl]-1,2,4-oxadiazol-3-yl}-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine

HRID 341459Notes

Reaction equation

HRID 341459 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.F[C:14]1[C:15]([C:20]([OH:22])=O)=[N:16][CH:17]=[CH:18][CH:19]=1.[NH2:23][C:24]1[N:29]=[C:28]([N:30]([CH3:38])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33](C)[CH:32]=2)[N:27]=[C:26]([C:39]([NH:41]O)=[NH:40])[N:25]=1.[CH:43]1([NH2:46])[CH2:45][CH2:44]1>N1C=CC=CC=1.CCOC(C)=O>[CH:43]1([NH:46][C:14]2[C:15]([C:20]3[O:22][N:40]=[C:39]([C:26]4[N:27]=[C:28]([N:30]([CH3:38])[C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:29]=[C:24]([NH2:23])[N:25]=4)[N:41]=3)=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:45][CH2:44]1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 69828CyclopropylamineHCID 27627863-Fluoropyridine-2-carboxylic acidHCID 1784255374-amino-N-hydroxy-6-(methyl-3-methylphenyl-amino)-[1,3,5]triazine-2-carboxamidine2×

Product 1

HCID 668028666-{5-[3-(Cyclopropylamino)pyridin-2-yl]-1,2,4-oxadiazol-3-yl}-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamineYield 17%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,1′-Carbonyldiimidazole (62 mg, 0.380 mmol) was added to a solution of 3-fluoropyridine-2-carboxylic acid (50 mg, 0.354 mmol) in anhydrous pyridine (1 mL) in a sealed tube at room temperature and the mixture was stirred for 1 h. 4-Amino-N-hydroxy-6-(methyl-3-methylphenyl-amino)-[1,3,5]triazine-2-carboxamidine (prepared in an analogous manner to Intermediate 1, 66 mg, 0.253 mmol) was added and the mixture was stirred at room temperature for 60 min and then at 90 C for approximately 18 h. The mixture was then treated with cyclopropanamine (300 μL, 4.32 mmol) and stirred at 80 C for 7 h. The mixture was then diluted with EtOAc (35 mL) and washed with water (10 mL), saturated aq. ammonium chloride (2×6 mL) and 2M hydrochloric acid (3×5 mL). The combined hydrochloric acid extractions were washed with DCM (2×6 mL) and then made alkaline by the addition of 2M aq. sodium hydroxide. The resulting solution was extracted with DCM (4×7 mL), the combined organic extractions were washed with brine (10 mL), dried over sodium sulfate and evaporated under vacuum. The crude residue was purified by flash chromatography (0-3% MeOH in DCM) to afford the title compound (17 mg, 17%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 60 min
  3. waitat 90 C for approximately 18 h
  4. stirringstirred at 80 C for 7 h
  5. washwashed with water (10 mL), saturated aq. ammonium chloride (2×6 mL) and 2M hydrochloric acid (3×5 mL)
  6. extractionThe combined hydrochloric acid extractions
  7. washwere washed with DCM (2×6 mL)
  8. additionby the addition of 2M aq. sodium hydroxide
  9. extractionThe resulting solution was extracted with DCM (4×7 mL)
  10. extractionthe combined organic extractions
  11. washwere washed with brine (10 mL)
  12. dry with materialdried over sodium sulfate
  13. customevaporated under vacuum
  14. customThe crude residue was purified by flash chromatography (0-3% MeOH in DCM)

Sources & evidence

ORD record
ord-722f728511ff48cfa66991e85d0e0f03
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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