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

반응식

HRID 43010 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 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)촉매HCID 8028Tetrahydrofuran용매3회HCID 10340Sodium Carbonate용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9ab4da0f9e864b2b9b46c206073c9c7d
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536214B2

연결된 노트

불러오는 중…