Triphenylphosphine → (S)-N-(5-((1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 43010

Reaction equation

HRID 43010 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[C:38]3[C:42](=[CH:43][CH:44]=2)[CH2:41][C@H:40]([NH:45][S:46]([CH:49]([CH3:51])[CH3:50])(=[O:48])=[O:47])[CH2:39]3)O1.Cl[CH2:54][C:55]1[N:59]([CH2:60][CH3:61])[N:58]=[C:57]([C:62]([F:65])([F:64])[F:63])[CH:56]=1>C1COCC1.C([O-])([O-])=O.[Na+].[Na+].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.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH2:60]([N:59]1[C:55]([CH2:54][C:36]2[CH:37]=[C:38]3[C:42](=[CH:43][CH:44]=2)[CH2:41][C@H:40]([NH:45][S:46]([CH:49]([CH3:50])[CH3:51])(=[O:47])=[O:48])[CH2:39]3)=[CH:56][C:57]([C:62]([F:64])([F:63])[F:65])=[N:58]1)[CH3:61]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 252477555-(chloromethyl)-1-ethyl-3-(trifluoromethyl)-1H-pyrazoleHCID 46899977(S)-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 44555671(S)-N-(5-((1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 6.4%

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 8028TetrahydrofuranSolvent3×HCID 10340Sodium CarbonateSolvent

Conditions

Temperature
100 °C

Procedure

Tris(dibenzylideneacetone)dipalladium (0) chloroform adduct (0.014 mmol, 14.17 mg) was dissolved in THF (1 mL) and triphenylphosphine (0.027 mmol, 7.18 mg) added. The mixture was stirred at room temperature for 30 m before addition of N-bromosuccinimide (0.027 mmol, 4.87 mg). Stirring was continued for a further 30 min before addition of (S)—N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (0.137 mmol, 50 mg) in 500 μL THF, 5-(chloromethyl)-1-ethyl-3-(trifluoromethyl)-1H-pyrazole (0.137 mmol, 29.1 mg) in 500 μL THF and 2M Na2CO3 solution (2 mL). The mixture was heated to 100° C. for 10 min in the microwave before the mixture was filtered through a filter tip and concentrated to dryness. The residue was partitioned between DCM/Water and the organic phase collected and dried using a hydrophobic filter. TLC (1:1 EtOAc/Heptane) shows complex mix (see in process)—difficulty to assign product spot. The residue was purified using silica chromatography (20% EtOAc/Heptane) to give a residue which was further purified on basic HPLC to give the desired compound (3.6 mg, 8.7 μmol, 6.3%). MS (ESI): m/z [M−H]− 414.4.

Workup

  1. filtrationwas filtered through a filter tip
  2. concentrationconcentrated to dryness
  3. customThe residue was partitioned between DCM/Water
  4. customthe organic phase collected
  5. customdried
  6. additionmix (
  7. customThe residue was purified
  8. customto give a residue which
  9. customwas further purified on basic HPLC

Sources & evidence

ORD record
ord-9ab4da0f9e864b2b9b46c206073c9c7d
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Linked notes

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