Methanol → HCID 68580211, compound

HRID 2233952Notes

Reaction equation

HRID 2233952 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])OC(C)(C)C)[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[CH3:22][OH:23].[Br:24][C:25]1[CH:26]=[C:27](C(OC2C(F)=C(F)C(F)=C(F)C=2F)=O)[NH:28][C:29]=1[CH3:30]>C[O-].[Na+]>[Br:24][C:25]1[CH:26]=[C:27]([C:15]([NH:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([O:23][CH3:22])[N:7]=3)[CH2:13][CH2:12]2)=[O:21])[NH:28][C:29]=1[CH3:30]

Participants

5

Reactant 3

HCID 887MethanolHCID 53486081HCID 53486081, compound2×HCID 86608241Pentafluorophenyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate2×

Product 1

HCID 68580211HCID 68580211, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 10942334Sodium MethoxideSolvent

Procedure

tert-Butyl [1-(6-chloropyridin-2-yl)piperidin-4-yl]carbamate (Intermediate 66) (300 mg, 0.99 mmol) was dissolved in 0.5 M solution of sodium methoxide in MeOH (9 ml, 4.45 mmol) at room temperature and the mixture was refluxed for 72 h. The solvent was removed in vacuo, extracted with EtOAc then washed with water. The organic phase was concentrated in vacuo and treated with 4 N hydrochloric acid in dioxane (10 ml) for 2 h. The solvent was removed in vacuo and dried to remove excess hydrochloric acid. The solid was dissolved in NMP (3 ml) and pentafluorophenyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate (Intermediate 17) (80 mg, 0.216 mmol) and TEA (137 μl, 0.9 mmol) were added. The mixture was stirred at room temperature for 2 h and the mixture was purified by semi-preparative HPLC using a gradient of 15-95% CH3CN/H2O (0.1% TFA) to give the title compound (23 mg).

Workup

  1. temperaturethe mixture was refluxed for 72 h
  2. customThe solvent was removed in vacuo
  3. extractionextracted with EtOAc
  4. washthen washed with water
  5. concentrationThe organic phase was concentrated in vacuo
  6. additiontreated with 4 N hydrochloric acid in dioxane (10 ml) for 2 h
  7. customThe solvent was removed in vacuo
  8. customdried
  9. customto remove excess hydrochloric acid
  10. dissolutionThe solid was dissolved in NMP (3 ml)
  11. customthe mixture was purified by semi-preparative HPLC

Sources & evidence

ORD record
ord-c1c3bb3a3b4f4f598cd8763f766e0025
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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