Tetrahydrofuran → HCID 59152923, compound

HRID 2387554Notes

Reaction equation

HRID 2387554 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].[Br-].[CH:33]1([Zn+])[CH2:37][CH2:36][CH2:35][CH2:34]1.O1CCCC1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>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]>[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]([CH:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[CH:21]=3)(=[O:19])=[O:18])[CH3:16])[C:9]=2[CH:8]=[N:7]1)[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 44611514HCID 44611514, compoundHCID 178419768HCID 178419768, compound

Product 1

HCID 59152923HCID 59152923, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Conditions

Temperature
50 °C

Procedure

To a mixture 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) (290 mg, 0.556 mmol) and a solution of cyclopentylzinc bromide in tetrahydrofuran (0.5 M, 10.0 mL, 5.0 mmol), bis(dibenzylideneacetone)palladium(0) (16.7 mg, 0.028 mmol) and tris(tert-butyl)phosphine (178 μL, 0.056 mmol) were added under an argon atmosphere. After being stirred at 50° C. for 1 hour, the mixture was concentrated in vacuo. Saturated ammonium chloride was added and the mixture was extracted with ethyl acetate (20 mL×3). The organic layers were combined, washed with saturated ammonium chloride, dried over sodium sulfate and concentrated in vacuo to afford {(R)-4-[(3-cyclopentyl-5-trifluoromethyl-benzene-sulfonyl)-methyl-amino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester (220 mg, 77%) as a viscous oil which was used for the next step without any purification. MS cald. for C24H30F3N3O4S 513, obsd. (ESI+) [(M+H)+] 514.

Workup

  1. customprepared by the method analogous to the one
  2. concentrationthe mixture was concentrated in vacuo
  3. additionSaturated ammonium chloride was added
  4. extractionthe mixture was extracted with ethyl acetate (20 mL×3)
  5. washwashed with saturated ammonium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-15af2d1f9a9a4e55adf93e5674cba648
Source dataset
uspto-grants-2012_09
Patent number
US08268870B2

Reaction notes

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