Morpholine → HCID 59631135, compound

HRID 1431449Notes

Reaction equation

HRID 1431449 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][C:21]([F:26])=[CH:22][C:23]=3[F:25])[N:18]=[C:17]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)[C:16]=2[CH3:33])[C:5]([C:8]2[CH2:9][CH2:10][O:11][CH2:12][CH:13]=2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.[NH:68]1[CH2:73][CH2:72][O:71][CH2:70][CH2:69]1.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]>[O:11]1[CH2:12][CH:13]=[C:8]([C:5]2[C:4]([NH:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([F:26])=[CH:22][C:23]=4[F:25])[N:18]=[C:17]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[C:16]=3[CH3:33])=[CH:3][C:2]([N:68]3[CH2:73][CH2:72][O:71][CH2:70][CH2:69]3)=[CH:7][N:6]=2)[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 59631138HCID 59631138, compoundHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 59631135HCID 59631135, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(5-bromo-2-(3,6-dihydro-2H-pyran-4-yl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine (35.5 mg, 0.07 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (7.1 mg, 0.015 mmol), tris(dibenzylideneacetone)dipalladium (0) (6.9 mg, 7.54 μmol), morpholine (0.05 mL, 0.57 mmol), and sodium tert-butoxide (20.7 mg, 0.215 mmol) in dry toluene (2.0 mL) was degassed by nitrogen. The mixture was heated to 100° 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 light orange film was purified by HPLC 10-60% 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-(3,6-dihydro-2H-pyran-4-yl)-5-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. Mass Spectrum (pos.) m/e: 516.3 (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
  7. customthe light orange film was purified by HPLC 10-60% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution
  8. concentrationThe desired fractions were concentrated
  9. additionthen diluted with EtOAc
  10. washAfter washing twice with satd aq. sodium bicarbonate solution and once with brine
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-31ad6ee693b9430fa328fd930da7eeda
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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