Potassium Carbonate → HCID 46842007, compound

HRID 1846351Notes

Reaction equation

HRID 1846351 reaction equation
[C:1]([O-])([O-])=O.[K+].[K+].CB1OB(C)OB(C)O1.Cl[C:17]1[N:22]=[CH:21][C:20]([C:23]2[N:32]([C:33]3[CH:38]=[CH:37][C:36]([CH:39]4[CH2:43][CH2:42][CH2:41][CH2:40]4)=[CH:35][CH:34]=3)[C:31](=[O:44])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)=[CH:19][CH:18]=1>O1CCOCC1.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>[CH:39]1([C:36]2[CH:37]=[CH:38][C:33]([N:32]3[C:31](=[O:44])[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]=[C:23]3[C:20]3[CH:21]=[N:22][C:17]([CH3:1])=[CH:18][CH:19]=3)=[CH:34][CH:35]=2)[CH2:40][CH2:41][CH2:42][CH2:43]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86659813HCID 86659813, compound

Product 1

HCID 46842007HCID 46842007, compoundYield 27.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

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. temperatureheated
  2. temperatureto reflux temperature for 20 minutes
  3. filtrationThe reaction mixture was filtered through Celite®
  4. washwashed with EtOAc
  5. concentrationThe filtrate was concentrated
  6. custompurified by flash chromatography on silica gel
  7. washeluting with 30% to 100% EtOAc in heptane

Sources & evidence

ORD record
ord-fa716506d39c404bb4c78bfb23f3c3b2
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

Loading…