Hydrochloric Acid → HCID 59152879, compound

HRID 1645171Notes

Reaction equation

HRID 1645171 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([S:17]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22](Br)[CH:21]=3)(=[O:19])=[O:18])[CH3:16])[C:9]=2[CH:8]=[N:7]1)[CH3:2].C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:51]([O:53]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:52].Cl>CN(C)C=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([S:17]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:51](=[O:53])[CH3:52])[CH:21]=3)(=[O:19])=[O:18])[CH3:16])[C:9]=2[CH:8]=[N:7]1)[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11773TriphenylarsineHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 44611514HCID 44611514, compound

Product 1

HCID 59152879HCID 59152879, compoundYield 86.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of {(R)-4-[(3-bromo-5-trifluoromethyl-benzenesulfonyl)-methyl-amino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester (example 2-5) (prepared by the method analogous to the one described for example 2-1) (1.0 g, 1.9 mmol) in N,N-dimethylformamide (8 mL) was added tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (175 mg, 0.19 mmol), triphenylarsine (Ph3As) (175 mg, 5.72 mmol) and 1-ethoxy-vinyltributyltin (1 mL, 2.86 mmol). After being stirred at 80° C. for 2 hours under an argon atmosphere, the reaction mixture was cooled to room temperature, 4N hydrochloric acid (1 mL) was added, and the mixture was stirred at room temperature for 20 minutes. The resulting mixture was poured into water (40 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), and then concentrated in vacuo. The residue was purified by flash column (gradient elution: 15-30% ethyl acetate in petroleum ether) to afford {(R)-4-[(3-acetyl-5-trifluoromethyl-benzenesulfonyl)-methyl-amino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester as a yellow oil (800 mg, 86.4%). MS cald. for C21H24F3N3O5S 487, obsd. (ESI+) [(M+H)+] 488.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature for 20 minutes
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column (gradient elution: 15-30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-002bad40ed444e9da77ac014ddf76f3d
Source dataset
uspto-grants-2012_02
Patent number
US08124641B2

Reaction notes

Loading…