Triethylamine → HCID 86643707, compound

HRID 1672851Notes

Reaction equation

HRID 1672851 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[C:11]([C:12](O)=[S:13])=[C:10]([Cl:15])[N:9]=[C:8]([CH3:16])[N:7]=1.C(N(CC)CC)C.[C:24]([O:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[CH2:36][NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([C:44]2[O:45][C:46](=[O:50])[N:47]([CH3:49])[N:48]=2)[CH:39]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>C(OCC)(=O)C.O.C1COCC1.CN(C=O)C>[C:24]([O:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[CH2:36][N:37]([C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([C:44]2[O:45][C:46](=[O:50])[N:47]([CH3:49])[N:48]=2)[CH:39]=1)[C:12]([C:11]1[C:10]([Cl:15])=[N:9][C:8]([CH3:16])=[N:7][C:6]=1[Cl:5])=[S:13])=[O:30])([CH3:27])([CH3:26])[CH3:25]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 67350930HCID 67350930, compoundHCID 178432883HCID 178432883, compound

Product 1

HCID 86643707HCID 86643707, compoundYield 163.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Thionyl chloride (15.7 mL, 215 mmol) and DMF (1 mL) were added to 4,6-dichloro-2-methylthio-pyrimidine-5-carboxylic acid (5.15 g, 21.5 mmol) obtained in Reference Example 4, and the mixture was stirred at 80° C. for 4 hours. The mixture was concentrated under reduced pressure, and the residue was dried for 12 hours under reduced pressure. The resulting residue was dissolved in THF (8 mL), and the mixture was stirred at room temperature for 1 hour after adding triethylamine (1.02 mL, 7.30 mmol), and a THF (10 mL) solution of (S)-1-tert-butoxycarbonyl-2-{N-[3-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]aminomethyl}pyrrolidine (1.37 mmol, 3.65 mmol) obtained in Step 5. The mixture was further stirred at 60° C. for 5.5 hours, and then for 6 hours under reflux. Water and ethyl acetate were added to the mixture to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was then purified by silica gel column chromatography to give (S)—N-(1-tert-butoxycarbonyl-pyrrolidin-2-ylmethyl)-4,6-dichloro-N-[3-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]-2-methylthiopyrimidine-5-carboxamide (1.30 g, 60%).

Workup

  1. customobtained in Reference Example 4
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was dried for 12 hours under reduced pressure
  4. dissolutionThe resulting residue was dissolved in THF (8 mL)
  5. stirringthe mixture was stirred at room temperature for 1 hour
  6. stirringThe mixture was further stirred at 60° C. for 5.5 hours
  7. temperaturefor 6 hours under reflux
  8. customto separate the organic layer
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe resulting residue was then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-01b5d941eaa5495e8b84b72e00211c73
Source dataset
uspto-grants-2011_08
Patent number
US07998954B2

Reaction notes

Loading…