4-Aminopyridine → HCID 135939044, compound

HRID 591705Notes

Reaction equation

HRID 591705 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=3[O:19][CH3:20])[N:9]=2)=[CH:4][CH:3]=1.[NH2:23][C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][O:19][C:14]1[CH:13]=[C:12]([O:21][CH3:22])[CH:11]=[C:10]2[C:15]=1[C:16](=[O:18])[NH:17][C:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[CH:3][CH:4]=1)=[N:9]2

Participants

8

Reactant 4

HCID 17274-AminopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 136348046HCID 136348046, compound

Product 1

HCID 135939044HCID 135939044, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of compound 2-(4-bromophenyl)-5,7-dimethoxyquinazolin-4(3H)-one) (0.200 g, 0.554 mmol), 4-aminopyridine (0.0573 g, 0.609 mmol), Pd2(dba)3 (0.0025 g, 0.0028 mmol), Xantphos (0.0018 g, 0.0031 mmol), and Cs2CO3 (0.253 g, 0.776 mmol) in 1,4-dioxane (2.22 mL) under nitrogen was heated at 105° C. for 2 days. The mixture was cooled to room temperature, diluted with EtOAc (200 mL), washed with water (3×75 mL), then brine (75 mL), dried over anhydrous Na2SO4, filtered, and the solvent was removed under vacuum. The resulting residue was purified over silica gel (12 g, EtOAc/CHCl3/MeOH/NH4OH), to provide the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6): δ 11.90 (s, 1H), 9.19 (s, 1H), 8.29 (d, J=6.29 Hz, 2H), 8.17 (d, J=8.75 Hz, 2H), 7.30 (d, J=8.75 Hz, 2H), 7.05 (d, J=6.29 Hz, 2H), 6.72 (d, J=2.26 Hz, 1H), 6.51 (d, J=2.26 Hz, 1H), 3.89 (s, 3H), 3.85 (s, 3H). MS (ESI) m/z 375 [C21H18N4O3+H]+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with water (3×75 mL)
  3. dry with materialbrine (75 mL), dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed under vacuum
  6. customThe resulting residue was purified over silica gel (12 g, EtOAc/CHCl3/MeOH/NH4OH)

Sources & evidence

ORD record
ord-530e2cdad59549658c5f06608f1ea931
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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