Dimethylformamide → HCID 18377283, compound

HRID 2301093Notes

Reaction equation

HRID 2301093 reaction equation
C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.[C:12]([O:16][C:17]([NH:19][CH2:20][CH:21]1[N:26]([C:27](=O)[CH2:28]Cl)[C:25]2[CH:31]=[CH:32][CH:33]=[CH:34][C:24]=2[S:23][CH2:22]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>O>[C:12]([O:16][C:17]([N:19]1[CH2:28][CH2:27][N:26]2[CH:21]([CH2:22][S:23][C:24]3[CH:34]=[CH:33][CH:32]=[CH:31][C:25]=32)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 18377348HCID 18377348, compound

Product 1

HCID 18377283HCID 18377283, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A 13.47 g (97.43 mmol) portion of potassium carbonate was added to DMF solution (360 ml) containing 11.59 g (32.48 mmol) of 3-(t-butoxycarbonyl)aminomethyl-4-chloroacetyl-3,4-dihydro-2H-1,4-benzthiazine and stirred at room temperature overnight and then at 60° C. for 3 hours. This was returned to room temperature, mixed with cool water and extracted with ethyl acetate. The extract was dried (Na2SO4) and then concentrated under a reduced pressure. The thus dried residue under a reduced pressure was dissolved in 180 ml of tetrahydrofuran and cooled to 0° C. This was mixed with 4.48 ml (48.72 mmol) of borane-dimethyl sulfide complex and stirred at 0° C. for 2 hours and then at room temperature for 2 hours. Cool water was added dropwise to the reaction solution which was subsequently stirred for 30 minutes and then extracted with ethyl acetate. The extract was washed with dilute hydrochloric acid and dried (Na2SO4), and then the solvent was removed by evaporation under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (650 cc; elution by ethyl acetate-hexane=1:4) and further recrystallized from ethyl acetate-hexane to obtain 5.04 g of the title compound (51% in yield).

Workup

  1. waitat 60° C. for 3 hours
  2. customThis was returned to room temperature
  3. extractionextracted with ethyl acetate
  4. dry with materialThe extract was dried (Na2SO4)
  5. concentrationconcentrated under a reduced pressure
  6. dissolutionThe thus dried residue under a reduced pressure was dissolved in 180 ml of tetrahydrofuran
  7. temperaturecooled to 0° C
  8. additionThis was mixed with 4.48 ml (48.72 mmol) of borane-dimethyl sulfide complex
  9. stirringstirred at 0° C. for 2 hours
  10. waitat room temperature for 2 hours
  11. stirringwas subsequently stirred for 30 minutes
  12. extractionextracted with ethyl acetate
  13. washThe extract was washed with dilute hydrochloric acid
  14. dry with materialdried (Na2SO4)
  15. customthe solvent was removed by evaporation under a reduced pressure
  16. customThe thus obtained residue was purified by a silica gel column chromatography (650 cc; elution by ethyl acetate-hexane=1:4)
  17. customfurther recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-85f5dee64b5948f7a196e7a79635cce2
Source dataset
uspto-grants-2002_12
Patent number
US06498251B1

Reaction notes

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