Toluene → HCID 49820277, compound

HRID 391305Notes

Reaction equation

HRID 391305 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-89765f1ac1884b06ada96c6d6f8ad01a
Source dataset
uspto-grants-2013_02
Patent number
US08383827B2

Reaction notes

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