2-(2-Methoxyphenyl)-3-pyridinamine → HCID 59631332, compound

HRID 1431443Notes

Reaction equation

HRID 1431443 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:14]([NH2:15])=[CH:13][CH:12]=[CH:11][N:10]=1.Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([F:28])=[CH:24][C:25]=2[F:27])[N:20]=[C:19]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[C:18]=1[CH3:35].C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:27][C:25]1[CH:24]=[C:23]([F:28])[CH:22]=[C:21]2[C:26]=1[C:17]([NH:15][C:14]1[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])=[N:10][CH:11]=[CH:12][CH:13]=1)=[C:18]([CH3:35])[C:19]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)=[N:20]2

Participants

7

Reactant 4

HCID 116441022-(2-Methoxyphenyl)-3-pyridinamineHCID 23676156Sodium t-butoxideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 59631332HCID 59631332, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(2-methoxyphenyl)-3-pyridinamine (30.8 mg, 0.15 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(2-pyridinyl)quinoline (67.8 mg, 0.23 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (15.5 mg, 0.03 mmol), tris(dibenzylideneacetone)dipalladium (0) (14.5 mg, 0.016 mmol), and sodium tert-butoxide (45.1 mg, 0.47 mmol) in dry toluene (2.0 mL) was degassed by nitrogen. The mixture was heated to 90° C. After 21.5 h, the reaction was cooled to rt, then treated with water. After extracting twice with EtOAc, the organic layers were combined and dried over anhydrous magnesium sulfate. After filtration and concentration the residue was purified on basic alumina (0-30% EtOAc in hexanes) to afford an light yellow solid as 5,7-difluoro-N-(2-(2-methoxyphenyl)-3-pyridinyl)-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.67 (1H, m), 8.31 (1H, d, J=4.5 Hz), 7.82 (1H, m), 7.70 (1H, m), 7.54 (3H, m), 7.30 (1H, m), 7.18 (1H, m), 7.06 (2H, t, J=7.5 Hz), 7.01 (1H, m), 6.87 (1H, ddd, J=13.2, 8.7, 2.0 Hz), 3.86 (3H, s), 1.82 (3H, br. s.). Mass Spectrum (pos.) m/e: 455.2 (M+1).

Workup

  1. customwas degassed by nitrogen
  2. temperaturethe reaction was cooled to rt
  3. additiontreated with water
  4. extractionAfter extracting twice with EtOAc
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration the residue
  7. customwas purified on basic alumina (0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9305841f8c49428a93490b1b94ff0fa4
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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