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 257569Notes

Reaction equation

HRID 257569 reaction equation
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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-29f2f42e66664d1f9068fac4d4a8bd22
Source dataset
uspto-grants-1993_11
Patent number
US05262412

Reaction notes

Loading…