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

反応式

HRID 43010 の反応式
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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 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)触媒HCID 8028Tetrahydrofuran溶媒3 回HCID 10340Sodium Carbonate溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-9ab4da0f9e864b2b9b46c206073c9c7d
出典データセット
uspto-grants-2013_09
特許番号
US08536214B2

関連ノート

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