6-Chloropyridine-3-carbaldehyde → HCID 86659813, compound

HRID 1846350Notes

Reaction equation

HRID 1846350 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=O)=[CH:4][CH:3]=1.[NH2:10][C:11]1[CH:30]=[CH:29][CH:28]=[CH:27][C:12]=1[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1)=[O:14]>CCO>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:18][CH:17]=3)[C:13](=[O:14])[C:12]3[C:11](=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:10]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 27640536-Chloropyridine-3-carbaldehydeHCID 86659814HCID 86659814, compound

Product 1

HCID 86659813HCID 86659813, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-chloro-3-pyridinecarboxaldehyde (0.177 g, 1.20 mmol) and CuCl2 (0.335 g, 2.40 mmol) were added to a solution of 2-amino-N-(4-cyclopentylphenyl)benzamide (0.350 g, 1.20 mmol) in EtOH (30 mL), and refluxed for 5 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in EtOAc. The organics were washed with H2O, then brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 15% to 60% EtOAc in heptane, afforded 2-(6-chloropyridin-3-yl)-3-(4-cyclopentylphenyl)quinazolin-4(3H)-one (0.260 g, 54%). Pd(PPh3)4 (0.150 g, 0.12 mmol), K2CO3 (0.270 g, 1.90 mmol), and trimethylboroxine (0.18 mL, 1.20 mmol) were added to a solution of 2-(6-chloropyridin-3-yl)-3-(4-cyclopentylphenyl)quinazolin-4(3H)-one (0.260 g, 0.65 mmol) in dioxane (15 mL) and heated to reflux temperature for 20 minutes. The reaction mixture was filtered through Celite®, washed with EtOAc. The filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 30% to 100% EtOAc in heptane, to afford the title compound as a white solid (0.068 g, 27%). 1H-NMR (300 MHz, DMSO-d6): δ8.45 (s, 1H), 8.19 (d, J=7.4 Hz, 1H), 7.84-8.00 (m, 1H), 7.78 (d, J=7.9 Hz, 1H), 7.50-7.70 (m, 2H), 7.17-7.31 (m, 4H), 7.11 (d, J=8.0 Hz, 1H), 2.85-3.06 (m, 1H), 2.38 (s, 3H), 1.85-2.09 (m, 2H), 1.34-1.84 (m, 6H). MS (APCI) m/z: 382 (M+H)+.

Workup

  1. temperaturerefluxed for 5 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in EtOAc
  4. washThe organics were washed with H2O
  5. dry with materialbrine, dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel
  9. washeluting with 15% to 60% EtOAc in heptane

Sources & evidence

ORD record
ord-d685f59047ec4ce884a3181e4fca962b
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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