Hydrochloric Acid → HCID 70654524, compound

HRID 2178188Notes

Reaction equation

HRID 2178188 reaction equation
C(=[N:14][C:15]1[CH:16]=[CH:17][C:18]([F:57])=[C:19]([C:21]2([CH:54]([F:56])[F:55])[CH2:27][CH2:26][S:25](=[O:29])(=[O:28])[CH2:24][C:23]([NH:30]C(C3C=CC(OC)=CC=3)(C3C=CC(OC)=CC=3)C3C=CC=CC=3)=[N:22]2)[CH:20]=1)(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.C(=N)(C1C=CC=CC=1)C1C=CC=CC=1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O1CCOCC1>[NH2:14][C:15]1[CH:16]=[CH:17][C:18]([F:57])=[C:19]([C:21]2([CH:54]([F:56])[F:55])[CH2:27][CH2:26][S:25](=[O:29])(=[O:28])[CH2:24][C:23]([NH2:30])=[N:22]2)[CH:20]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 136809Benzophenone imineHCID 86670222HCID 86670222, compound

Product 1

HCID 70654524HCID 70654524, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of {(RS)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-difluoromethyl-1,1-dioxo-2,5,6,7-tetrahydro-1H-1λ6-[1,4]thiazepin-3-yl}-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amine (207 mg, 263 μmol) in dichloromethane (10 ml) was treated with trifluoroacetic acid (1.01 ml, 13.1 mmol). The orange colored solution was stirred at room temperature for 1 hour. In order to cleave the intermediate benzophenonimine, hydrochloric acid (1M, 2.63 ml) and dioxane (10 ml) were added. The mixture was stirred at 23° C. for 4 hours. For the workup, the reaction mixture was poured into an aqueous solution of sodium carbonate (1 M) followed by the extraction with dichloromethane. The organic layer was washed with brine, dried over sodium sulfate and evaporated. The crude product was purified by chromatography on silica gel using a 110:10:1-mixture of dichloromethane, methanol and ammonium hydroxide as the eluent. The (RS)-5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-1,1-dioxo-2,5,6,7-tetrahydro-1H-1λ6-[1,4]thiazepin-3-ylamine (72 mg, 85% yield) was obtained as a light brown foam. MS (ISP): m/z=322.0 [M+H]+.

Workup

  1. additionwere added
  2. stirringThe mixture was stirred at 23° C. for 4 hours
  3. extractionfollowed by the extraction with dichloromethane
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe crude product was purified by chromatography on silica gel using a 110:10

Sources & evidence

ORD record
ord-983737979fcd4b42bf4dc1fb69617e92
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

Loading…