Toluene → HCID 49820277, compound

HRID 1897789Notes

Reaction equation

HRID 1897789 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[CH:6]=[N:7][CH:8]=1)=O.[CH2:17]([S:19]([NH2:22])(=[O:21])=[O:20])[CH3:18].[NH4+].[Cl-].[C:25]1([CH3:31])C=CC=C[CH:26]=1>C(OCC)(=O)C.[Cl-].[Na+].O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:13]([C:12]1[CH:15]=[CH:16][C:9]([C:5]2[CH:4]=[C:3]([CH:1]([CH:31]3[CH2:25][CH2:26]3)[NH:22][S:19]([CH2:17][CH3:18])(=[O:21])=[O:20])[CH:8]=[N:7][CH:6]=2)=[CH:10][CH:11]=1)#[N:14]

Participants

8

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 73702EthanesulfonamideHCID 595784114-(5-Formylpyridin-3-yl)benzonitrile

Product 1

HCID 49820277HCID 49820277, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-36 °C

Procedure

Titanium isopropoxide (0.70 mL, 2.40 mmol) was added to a mixture of 4-(5-formyl-pyridin-3-yl)-benzonitrile (250 mg, 1.20 mmol) and ethanesulfonamide (144 mg, 1.32 mmol) in toluene (10 mL) at room temperature. The resulting mixture was heated to reflux for 2 h. After concentration, the residue was dissolved in THF (10 mL) and cooled to −40° C. c-PrMgBr (0.5 M in THF, 12.0 mL, 6.00 mmol) was added dropwise and the resulting mixture was stirred at −36° C. for 1 h. Saturated NH4Cl solution was then added to the reaction mixture. The resulting solution was diluted with ethyl acetate and brine. The mixture was filtered and the organic layer was separated. After concentration, the residue was purified by flash column (MeOH/DCM, v/v, 0-3%) to give N-((5-(4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide (210 mg, 51%); ESI-MS m/z: 342 [M+1]+, 1H-NMR (MeOD, 400 MHz) δ 8.83 (d, J=2.0 Hz, 1H), 8.69 (d, J=2.0 Hz, 1H), 8.24 (t, J=2.0 Hz, 1H), 7.92 (s, 4H), 3.96 (d, J=9.2 Hz, 1H), 3.06-2.93 (m, 2H), 1.35-1.31 (m, 1H), 1.31 (t, J=7.2 Hz, 3H), 0.81-0.76 (m, 1H), 0.67-0.61 (m, 2H), 0.54-0.49 (m, 1H); enantiomers were separated by chiral HPLC (Chiralpak IA-H, EtOH/Heptane, v/v, 70/30) to the first peak (enantiomer 1, t=10.20 min) and the second peak (enantiomer 2, t=15.99 min).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 2 h
  3. concentrationAfter concentration
  4. dissolutionthe residue was dissolved in THF (10 mL)
  5. additionwas added dropwise
  6. filtrationThe mixture was filtered
  7. customthe organic layer was separated
  8. concentrationAfter concentration
  9. customthe residue was purified by flash column (MeOH/DCM, v/v, 0-3%)

Sources & evidence

ORD record
ord-a6efdae02c1943d4908cdabf85ddb95a
Source dataset
uspto-grants-2013_08
Patent number
US08519142B2

Reaction notes

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