Toluene → 3-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-1-[2-chloro-5-(propionylamino)phenyl]-1H-pyrazole-5-carbonitrile

HRID 257569노트

반응식

HRID 257569 반응식
Br[C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[C:8]([CH2:26][CH2:27][CH2:28][CH3:29])=[N:9][N:10]([C:14]3[CH:19]=[C:18]([NH:20][C:21](=[O:24])[CH2:22][CH3:23])[CH:17]=[CH:16][C:15]=3[Cl:25])[C:11]=2[C:12]#[N:13])=[C:4]([F:32])[CH:3]=1.C1(C)C=CC=CC=1.[C:40]([NH:44][S:45]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1B(O)O)(=[O:47])=[O:46])([CH3:43])([CH3:42])[CH3:41].[OH-].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCCCCC.CCOC(C)=O>[CH2:26]([C:8]1[C:7]([CH2:6][C:5]2[CH:30]=[CH:31][C:2]([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=3[S:45](=[O:47])(=[O:46])[NH:44][C:40]([CH3:41])([CH3:43])[CH3:42])=[CH:3][C:4]=2[F:32])=[C:11]([C:12]#[N:13])[N:10]([C:14]2[CH:19]=[C:18]([NH:20][C:21](=[O:24])[CH2:22][CH3:23])[CH:17]=[CH:16][C:15]=2[Cl:25])[N:9]=1)[CH2:27][CH2:28][CH3:29]

참가 물질

8

반응물 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 4997616Boronic acid, B-(2-(((1,1-dimethylethyl)amino)sulfonyl)phenyl)-HCID 19783143HCID 19783143, 화합물

생성물 1

HCID 197831473-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-1-[2-chloro-5-(propionylamino)phenyl]-1H-pyrazole-5-carbonitrile수율 77%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매2회HCID 21226206Ethyl acetate hexane용매

반응 조건

온도
90 °C

실험 절차

A reaction flask was charged with 155 mg (0.299 mmol) of 4-(4-bromo-2-fluorobenzyl)-3-n-butyl-1-[2-chloro-5-(propionylamino)phenyl]-1H-pyrazole-5-carbonitrile (from Step H), 3.5 mL of toluene, 2.4 mL of ethanol, 615 μL (0.598 mmol) of a 250 mg/mL solution of 2-(N-t-butylsulfamoyl)phenylboronic acid (from Step I) in ethanol, 950 μL (1.20 mmol) of 1.25N NaOH, and 17 mg of tetrakis(triphenylphosphine)palladium(0). The mixture was stirred under N2 at 90° C. for 5 hours, then cooled and concentrated. The residue was partitioned between 30 mL of ethyl acetate and 25 mL of H2O. The organic layer was washed with brine, dried (Na2SO4), filtered, and evaporated in vacuo. The yellow residual oil was flash chromatographed on silica gel (elution with 3:1 and then 1:1 hexane-EtOAc) to give a 77% yield of the title compound as a slightly yellow, stiff foam; homogeneous by TLC in 3:1 hexane-EtOAc; mass spectrum (FAB) m/e 650 (M+1)+. 400 MHz 1H NMR (CDCl3) δ0.92 (t, J=7.3 Hz, 3H), 100 (s, 9H), 1.21 (t, J=7.5 Hz, 3H), 1.38 (m, 2H), 1.65 (m, 2H), 2.39 (q, J=7.5 Hz, 2H), 2.66 (t, J=7.8 Hz, 2H), 3.98 (s, 1H), 4.02 (s, 2H), 7.2-7.6 (m, 8H), 7.82 (d, J=2.5 Hz, 1H), 8.15 (dd, J=7.9, 1.4 Hz, 1H).

후처리

  1. temperaturecooled
  2. concentrationconcentrated
  3. customThe residue was partitioned between 30 mL of ethyl acetate and 25 mL of H2O
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customchromatographed on silica gel (
  9. washelution with 3:1

출처 및 근거

ORD 기록
ord-29f2f42e66664d1f9068fac4d4a8bd22
출처 데이터셋
uspto-grants-1993_11
특허 번호
US05262412

반응 노트

불러오는 중…