4-(Trifluoromethyl)aniline → 7-Benzyl-N-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine

HRID 971228Notes

Reaction equation

HRID 971228 reaction equation
[CH2:1]([CH:8]1[C:17]2[C:12](=[C:13](Br)[N:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[Na+].[F:25][C:26]([F:35])([F:34])[C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1>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].C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH2:1]([CH:8]1[CH2:17][C:16]2[C:15]([NH:31][C:30]3[CH:32]=[CH:33][C:27]([C:26]([F:25])([F:34])[F:35])=[CH:28][CH:29]=3)=[N:14][CH:13]=[CH:12][C:11]=2[CH2:10][NH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 99644-(Trifluoromethyl)anilineHCID 23676156Sodium t-butoxideHCID 86602110Benzyl-5-bromo-1,2,3,4-tetrahydro-2,6-naphthyridine

Product 1

HCID 692212867-Benzyl-N-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amineYield 92%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178477754HCID 178477754, compoundCatalystHCID 1140TolueneSolvent

Procedure

Benzyl-5-bromo-1,2,3,4-tetrahydro-2,6-naphthyridine (see WO03/076427) (250 mg, 0.82 mmol) was dissolved in 1 mL of anhydrous toluene. To the mixture was added Pd2 (dba)3 (10 mol %, 85 mg) and PdCl2(DPPF) (33 mg, 5 mol %), followed by NaOtBu (118 mg, 1.23 mmol). After mixing for 5 min, 4-(trifluoromethyl)aniline (0.153 mL, 1.23 mmol) was added and the mixture was heated at 160° C. for 1200s in a Personal Chemistry microwave. The reaction mixture was filtered and the solvent was evaporated and the residue was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give a brown-purple residue. The residue was purified by flash chromatography over silica gel using a gradient of ethyl acetate:hexane (0-100%) to give the desired compound as an off-white powder (288 mg, 92%).

Workup

  1. additionAfter mixing for 5 min
  2. filtrationThe reaction mixture was filtered
  3. customthe solvent was evaporated
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed with saturated aqueous sodium bicarbonate and brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give a brown-purple residue
  10. customThe residue was purified by flash chromatography over silica gel using a gradient of ethyl acetate

Sources & evidence

ORD record
ord-06216e2ecee040088ccfcc9f5501cd95
Source dataset
uspto-grants-2007_12
Patent number
US07312330B2

Reaction notes

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