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 257569ノート

反応式

HRID 257569 の反応式
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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒2 回HCID 21226206Ethyl acetate hexane溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-29f2f42e66664d1f9068fac4d4a8bd22
出典データセット
uspto-grants-1993_11
特許番号
US05262412

反応ノート

読み込み中…