1,4-Cyclohexadiene → N-(2,6-dimethylphenyl)-4-[(4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)amino]benzamide

HRID 406851Notes

Reaction equation

HRID 406851 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10](=[O:41])[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2[N:19]=[C:20]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:21]3[CH2:27][CH2:26][N:25](CC4C=CC=CC=4)[CH2:24][C:22]=3[N:23]=2)=[CH:13][CH:12]=1.C1CC=CCC=1>[Pd].C(O)C>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[NH:9][C:10](=[O:41])[C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18]2[N:19]=[C:20]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:21]3[CH2:27][CH2:26][NH:25][CH2:24][C:22]=3[N:23]=2)=[CH:15][CH:16]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 57662921N-(2,6-dimethylphenyl)-4-{[4-phenyl-7-(phenylmethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl]amino}benzamide

Product 1

HCID 57662967N-(2,6-dimethylphenyl)-4-[(4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)amino]benzamideYield 62.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-(2,6-dimethylphenyl)-4-{[4-phenyl-7-(phenylmethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl]amino}benzamide (60 mg, 0.11 mmol), prepared as described in Example 249, 1,4-cyclohexadiene (11 μL, 0.11 mmol) and 10% palladium on carbon (8 mg) in ethanol (2 mL) were heated to 80° C. overnight. Upon cooling to rt, the reaction mixture was filtered through celite and concentrated on a rotary evaporator. The resulting residue was purified by preparative reverse phase HPLC to give N-(2,6-dimethylphenyl)-4-[(4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)amino]benzamide (31 mg, 62%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.87 (s, 1H), 9.52 (s, 1H), 7.96 (m, 4H), 7.62 (m, 2H), 7.52 (m, 3H), 7.11 (m, 3H), 3.75 (m, 2H), 3.05 (m, 2H), 2.79 (m, 2H), 2.17 (s, 6H). MS (EI) for C28H27N5O: 450.2 (MH+).

Workup

  1. customprepared
  2. temperatureUpon cooling to rt
  3. filtrationthe reaction mixture was filtered through celite
  4. concentrationconcentrated on a rotary evaporator
  5. customThe resulting residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-2696515adb6d4992bb1adc61fb0d27b9
Source dataset
uspto-grants-2014_06
Patent number
US08754092B2

Reaction notes

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