Hydrochloric Acid → HCID 59618735, compound

HRID 1691478Notes

Reaction equation

HRID 1691478 reaction equation
[F:1][C:2]([F:35])([F:34])[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[C:19]3[CH:20]=[C:21](C#N)[CH:22]=[CH:23][C:18]=3[NH:17][C:16]3[N:26]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:28]=[CH:29][C:15]=3[CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[CH3:36][Mg]Br.Cl.[C:40]([O-:43])(O)=O.[Na+]>C1COCC1>[F:35][C:2]([F:1])([F:34])[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[C:19]3[CH:20]=[C:21]([C:40](=[O:43])[CH3:36])[CH:22]=[CH:23][C:18]=3[NH:17][C:16]3[N:26]=[C:27]([C:30]([F:31])([F:32])[F:33])[CH:28]=[CH:29][C:15]=3[CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 86649044HCID 86649044, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59618735HCID 59618735, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbonitrile (702 mg, 1.365 mmol) in 5 ml of THF was added a solution of methyl magnesium bromide (4.87 ml, 6.82 mmol) in THF (1.4 M) at 0° C. The solution was heated to reflux for 8 h, then the solution was cooled to room temperature. Excess Grignard reagent was decomposed by the addition of 4 mL of 2N HCl and the solution was stirred for 1 hr at rt. The pH was adjusted to 7-8 with aqueous NaHCO3. The resulting solution was filtered and the solids were washed with CH2Cl2. To the filtrate was added 30 mL of CH2Cl2, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3×20 ml), and the combined organic layers were dried with Na2SO4 and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/ethyl acetate (6:1-4:1) to give the title compound as a white solid; Mass Spectrum: m/e=591 (M+1).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 8 h
  3. filtrationThe resulting solution was filtered
  4. washthe solids were washed with CH2Cl2
  5. additionTo the filtrate was added 30 mL of CH2Cl2
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with CH2Cl2 (3×20 ml)
  8. dry with materialthe combined organic layers were dried with Na2SO4
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with hexane/ethyl acetate (6:1-4:1)

Sources & evidence

ORD record
ord-eecfc14c00b1452da6ce68b07cd8c2cc
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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