3-Aminoquinoline → Quinolin-3-yl-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-amine

HRID 2105620Notes

Reaction equation

HRID 2105620 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[N:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOCC.C1(C)C=CC=CC=1>[N:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:28]=[C:19]([NH:18][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:20]=1

Participants

8

Reactant 4

HCID 113753-AminoquinolineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 288758632-Chloro-4-(4-trifluoromethylphenyl)pyridine

Product 1

HCID 57808192Quinolin-3-yl-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

To an oven-dried 50 m]L round-bottomed flask were added 2-chloro-4-(4-trifluoromethyl-phenyl)-pyridine (138 mg, 0.54 mmol) and 3-aminoquinoline (Aldrich Chemical Company) (93 mg, 0.64 mmol), followed by anhydrous toluene (45 mL). Nitrogen was bubbled through the above solution via a needle for 1h. Then palladium acetate (Aldrich Chemical Company) (18 mg, 0.08 mmol) and BINAP (Aldrich Chemical Company) (50 mg, 0.08 mmol) were added to the reaction in one portion, followed by sodium tert-butoxide (Aldrich Chemical Company) (145 mg, 1.5 mmol). The reaction mixture was heated at 90° C. overnight. After cooling to room temperature, the reaction mixture was taken up to ether, and washed with brine. The aqueous layer was extracted with ether (2x) and the combined ether layer was dried over Na2SO4 and concentrated. The residue was purified on a Biotage 40 S column (2.5:1 hexane:EtOAc) to give the title compound as an off-white solid. MS (ESI, pos. ion) m/z: 366 (M+1). Mp: 207.4-207.5° C.

Workup

  1. customNitrogen was bubbled through the above solution via a needle for 1h
  2. temperatureAfter cooling to room temperature
  3. washwashed with brine
  4. extractionThe aqueous layer was extracted with ether (2x)
  5. dry with materialthe combined ether layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified on a Biotage 40 S column (2.5:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-e75e328724c042b0b5dd752721a36a0b
Source dataset
uspto-grants-2009_08
Patent number
US07579347B2

Reaction notes

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