Methanol → HCID 178509263, compound

HRID 337767Notes

Reaction equation

HRID 337767 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:39]1[CH:44]=[CH:43][N:42]=[CH:41][N:40]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13]([O:17][C@H:18]2[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]2[C:24]2[C:25]([N+:35]([O-])=O)=[N:26][N:27](C3CCCCO3)[CH:28]=2)=[CH:12][C:11]=1[F:38])(=[O:9])=[O:8].[Cl-].[NH4+].C([SiH](CC)CC)C.CO>C(O)C.ClCCl.FC(F)(F)C(O)=O.[Fe]>[NH2:35][C:25]1[C:24]([C@H:19]2[CH2:20][CH2:21][CH2:22][CH2:23][C@@H:18]2[O:17][C:13]2[C:14]([F:16])=[CH:15][C:10]([S:7]([NH:6][C:39]3[CH:44]=[CH:43][N:42]=[CH:41][N:40]=3)(=[O:8])=[O:9])=[C:11]([F:38])[CH:12]=2)=[CH:28][NH:27][N:26]=1

Participants

9

Reactant 4

HCID 887MethanolHCID 12052TriethylsilaneHCID 25517Ammonium ChlorideHCID 89963403HCID 89963403, compound

Product 1

HCID 178509263HCID 178509263, compoundYield 21%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of the N-(2,4-dimethoxybenzyl)-2,5-difluoro-4-({(1S*,2R*)-2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]cyclohexyl}oxy)-N-(pyrimidin-4-yl)benzenesulfonamide (310 mg, 0.434 mmol) prepared in Example 34c, an iron powder (300 mg, 5.37 mol) and a saturated aqueous solution of ammonium chloride (5.0 mL) in ethanol (10 mL) was heated under reflux with stirring for 1 hour. After allowing to cool, the reaction solution was filtered through celite, and the filtrate was subjected to extraction with dichloromethane (100 mL). The organic layer was dried over anhydrous sodium sulfate and vacuum concentrated to yield crude amine. To a solution of the crude amine and triethylsilane (0.30 mL) in dichloromethane (3.0 mL), trifluoroacetic acid (3.0 mL) was added at room temperature, and the reaction solution was stirred for 1 hour. To the reaction solution, methanol (3.0 mL) was added, and the mixture was further stirred at room temperature for 1 hour. The reaction solution was concentrated, and the residue was purified with silica gel chromatography (dichloromethane/methanol=90:10) to yield the title compound (41.1 mg, 21%) as a colorless solid.

Workup

  1. temperatureunder reflux
  2. temperatureto cool
  3. filtrationthe reaction solution was filtered through celite
  4. extractionthe filtrate was subjected to extraction with dichloromethane (100 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate and vacuum
  6. concentrationconcentrated
  7. customto yield crude amine
  8. stirringthe reaction solution was stirred for 1 hour
  9. stirringthe mixture was further stirred at room temperature for 1 hour
  10. concentrationThe reaction solution was concentrated
  11. customthe residue was purified with silica gel chromatography (dichloromethane/methanol=90:10)

Sources & evidence

ORD record
ord-197c79c77339474b89ff79ce6fafcfa7
Source dataset
uspto-grants-2014_11
Patent number
US08889741B2

Reaction notes

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