Methyl iodide → HCID 67350924, compound

HRID 1672776Notes

Reaction equation

HRID 1672776 reaction equation
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[C:15](=[O:16])[N:14]([C:17]3[CH:18]=[N:19][CH:20]=[C:21]([CH:25]=3)C(O)=O)[CH2:13][CH:12]3[N:8]([CH2:9][CH2:10][CH2:11]3)[C:7]=2[N:26]=1.[C:27]([N:34]1[CH:38]=CN=C1)(N1C=CN=C1)=[O:28].[NH2:39]N.CI.[C:43](=[O:46])([O-])[O-].[K+].[K+]>ClCCl.C1COCC1.O>[CH3:38][N:34]1[N:39]=[C:43]([C:21]2[CH:20]=[N:19][CH:18]=[C:17]([N:14]3[CH2:13][C@H:12]4[N:8]([CH2:9][CH2:10][CH2:11]4)[C:7]4[N:26]=[C:3]([S:2][CH3:1])[N:4]=[CH:5][C:6]=4[C:15]3=[O:16])[CH:25]=2)[O:46][C:27]1=[O:28]

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 9321HydrazineHCID 11430Potassium CarbonateHCID 682631,1'-Carbonyldiimidazole2×HCID 86761392HCID 86761392, compound

Product 1

HCID 67350924HCID 67350924, compoundYield 45%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-5-[5-(9-Methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)nicotinic acid (200 mg, 0.538 mmol) obtained in Step 2 was dissolved in dichloromethane (5 mL), and the mixture was stirred at room temperature for 30 minutes after adding 1,1′-carbonyldiimidazole (96.0 mg, 0.592 mmol). The mixture was further stirred for 3 hours after adding hydrazine.monohydrate (0.0780 mL, 1.62 mmol), and concentrated under reduced pressure. The resulting residue was dissolved in THF (5 mL), and stirred therein at 60° C. for 2 hours after adding 1,1′-carbonyldiimidazole (0.288 g, 1.78 mmol). After cooling the mixture to room temperature, the precipitate was removed by filtration, and the filtrate was collected and concentrated. The resulting residue was dissolved in DMF (5 mL), and stirred therein at room temperature for 1.5 hours after adding methyl iodide (0.100 mL, 1.61 mmol) and potassium carbonate (222 mg, 1.61 mmol). Thereafter, water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was collected, washed with saturated brine, and dried over anhydrous magnesium sulfate. The residue obtained upon concentration under reduced pressure was then purified by silica gel column chromatography to give (S)-3-methyl-5-[5-(9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)pyridin-3-yl]-1,3,4-oxadiazol-2(3H)-one (102 mg, 45%).

Workup

  1. stirringThe mixture was further stirred for 3 hours
  2. stirringstirred
  3. temperatureAfter cooling the mixture to room temperature
  4. customthe precipitate was removed by filtration
  5. customthe filtrate was collected
  6. concentrationconcentrated
  7. dissolutionThe resulting residue was dissolved in DMF (5 mL)
  8. stirringstirred
  9. extractionthe mixture was extracted with ethyl acetate
  10. customThe organic layer was collected
  11. washwashed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe residue obtained upon concentration under reduced pressure
  14. customwas then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a5741d595ed044c9bcd1c01e27a62a60
Source dataset
uspto-grants-2011_08
Patent number
US07998954B2

Reaction notes

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