Ammonia → HCID 77014371, compound

HRID 538355Notes

Reaction equation

HRID 538355 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][N:12]=2)=[O:10])=[CH:4][C:3]=1[C:18]1([CH2:25][F:26])[CH2:23][O:22][CH2:21][C:20](=S)[NH:19]1.C(OO)(C)(C)C.[O-]S([O-])(=S)=O.[Na+].[Na+].[NH3:40]>CO>[ClH:1].[NH2:40][C:20]1[CH2:21][O:22][CH2:23][C:18]([C:3]2[CH:4]=[C:5]([NH:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][N:12]=3)=[O:10])[CH:6]=[N:7][C:2]=2[Cl:1])([CH2:25][F:26])[N:19]=1

Participants

6

Reactant 4

HCID 222Ammonia3×HCID 6410tert-Butyl hydroperoxideHCID 24477Sodium ThiosulfateHCID 86668065HCID 86668065, compound

Product 1

HCID 77014371HCID 77014371, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a suspension of 5-bromo-pyridine-2-carboxylic acid [6-chloro-5-(3-fluoromethyl-5-thioxo-morpholin-3-yl)-pyridin-3-yl]-amide (26 mg, 0.057 mmol) in 7M NH3 in MeOH (0.23 ml) was added at −20° C., tert.-butylhydroperoxide (0.055 ml, 0.566 mmol) and aq. 25% NH3 (0.15 ml, 0.99 mmol), the reaction mixture was stirred at room temperature for 80 min, 7M NH3 in MeOH (0.69 ml) were added and stirring continued for 20 h. At 0° C. halfsaturated aq. Na2S2O3 was added and the mixture extracted with EtOAc. The combined organic layers were washed with halfsaturated aq. NaCl, dried with Na2SO4 and evaporated. The residue was purified by preparative TLC DCM/MeOH 9:1 to yield the desired compound as colorless foam. The product was dissolved in DCM/MeOH, 5 equivalents of 5M HCl in Et2O were added and the solvents evaporated to provide the title compound as beige solid.

Workup

  1. additionwas added at −20° C.
  2. extractionthe mixture extracted with EtOAc
  3. washThe combined organic layers were washed with halfsaturated aq. NaCl
  4. dry with materialdried with Na2SO4
  5. customevaporated
  6. customThe residue was purified by preparative TLC DCM/MeOH 9:1

Sources & evidence

ORD record
ord-af7153ed06aa4575a600bba66bf940a3
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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