Triethylsilane → HCID 89963386, compound

HRID 337990Notes

Reaction equation

HRID 337990 reaction equation
[F:1][C:2]1([F:49])[CH2:7][C@H:6]([O:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([S:16]([N:19](CC3C=CC(OC)=CC=3OC)[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)(=[O:18])=[O:17])=[C:11]([F:37])[CH:10]=2)[C@@H:5]([C:38]2[N:42](COCCOC)[N:41]=[CH:40][CH:39]=2)[CH2:4][CH2:3]1.C([SiH](CC)CC)C>ClC(Cl)C.FC(F)(F)C(O)=O>[F:49][C:2]1([F:1])[CH2:7][C@H:6]([O:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([S:16]([NH:19][C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)(=[O:18])=[O:17])=[C:11]([F:37])[CH:10]=2)[C@@H:5]([C:38]2[NH:42][N:41]=[CH:40][CH:39]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 12052TriethylsilaneHCID 89963346HCID 89963346, compound

Product 1

HCID 89963386HCID 89963386, compoundYield 71.1%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of the 4-{[(1S*,2R*)-5,5-difluoro-2-{1-[(2-methoxyethoxy)methyl]-1H-pyrazol-5-yl}cyclohexyl]oxy}-N-(2,4-dimethoxybenzyl)-2-fluoro-5-methyl-N-(pyrimidin-4-yl)benzenesulfonamide (265 mg, 0.376 mmol) prepared in Example 155h and triethylsilane (0.50 mL) in dichloroethane (5.0 mL), trifluoroacetic acid (5.0 mL) was added at room temperature, and the reaction solution was stirred for 4 hours. The reaction solution was concentrated, then methanol (15 mL) and 6 M hydrochloric acid (5.0 mL) were added to the residue, and the reaction solution was stirred for 5 hours under heated reflux. To the reaction solution, an aqueous sodium hydrogencarbonate solution (50 mL) was added, followed by extraction five times with a dichloromethane/methanol (10:1) mixed solvent (50 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography (dichloromethane/methanol=10:1) to yield the title compound (125 mg, 71%) as a colorless solid.

Workup

  1. concentrationThe reaction solution was concentrated
  2. additionmethanol (15 mL) and 6 M hydrochloric acid (5.0 mL) were added to the residue
  3. stirringthe reaction solution was stirred for 5 hours
  4. temperatureunder heated
  5. temperaturereflux
  6. additionTo the reaction solution, an aqueous sodium hydrogencarbonate solution (50 mL) was added
  7. extractionfollowed by extraction five times with a dichloromethane/methanol (10:1)
  8. additionmixed solvent (50 mL)
  9. dry with materialThe thus obtained organic layer was dried over anhydrous sodium sulfate
  10. concentrationAfter vacuum concentration
  11. customthe residue was purified with silica gel chromatography (dichloromethane/methanol=10:1)

Sources & evidence

ORD record
ord-dbf2c5dad7df46fbb0e42abceab84b8d
Source dataset
uspto-grants-2014_11
Patent number
US08889741B2

Reaction notes

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