Sodium t-butoxide → HCID 59631438, compound

HRID 1431445Notes

Reaction equation

HRID 1431445 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][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])=[CH:11][N:10]=1.Cl[C:25]1[C:34]2[C:29](=[CH:30][C:31]([F:36])=[CH:32][C:33]=2[F:35])[N:28]=[C:27]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)[C:26]=1[CH3:43].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]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:14]([NH:15][C:25]2[C:34]3[C:29](=[CH:30][C:31]([F:36])=[CH:32][C:33]=3[F:35])[N:28]=[C:27]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[C:26]=2[CH3:43])=[CH:13][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 59631320HCID 59631320, compoundHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 59631438HCID 59631438, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2,5-bis(2-methoxyphenyl)-3-pyridinamine (37.5 mg, 0.12 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(2-pyridinyl)quinoline (54.7 mg, 0.19 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (12.1 mg, 0.025 mmol), tris(dibenzylideneacetone)dipalladium (0) (11.9 mg, 0.013 mmol), and sodium tert-butoxide (36.7 mg, 0.38 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 impure light yellow film. The film was further purified by HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions were concentrated then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a white solid as N-(2,5-bis(2-methoxyphenyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (500 MHz, CDCl3) δ ppm 8.69 (1H, d, J=4.6 Hz), 8.52 (1H, d, J=1.7 Hz), 7.84 (1H, td, J=7.7, 1.7 Hz), 7.76 (1H, d, J=7.6 Hz), 7.62 (2H, m), 7.50 (1H, m), 7.41 (4H, m), 7.16 (1H, t, J=7.5 Hz), 7.08 (1H, d, J=8.1 Hz), 7.04 (3H, m), 3.98 (3H, s), 3.83 (3H, s), 2.06 (3H, br. s.). Mass Spectrum ESI (pos.) m/e: 561.3 (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)
  8. customto afford an impure light yellow film
  9. customThe film was further purified by HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions
  10. concentrationwere concentrated
  11. additionthen diluted with EtOAc
  12. washAfter washing twice with satd aq. sodium bicarbonate solution and once with brine
  13. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-714f9cdf5a584fb78f9eea3171c402af
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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