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

HRID 2219954Notes

Reaction equation

HRID 2219954 reaction equation
C([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[N:13][C:14]=2Br)[CH2:9]1)C1C=CC=CC=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.[C:36]1([CH3:42])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=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]>[CH2:42]([CH:17]1[CH2:16][C:15]2[C:14]([NH:31][C:30]3[CH:32]=[CH:33][C:27]([C:26]([F:34])([F:35])[F:25])=[CH:28][CH:29]=3)=[N:13][CH:12]=[CH:11][C:10]=2[CH2:9][NH:8]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 99644-(Trifluoromethyl)anilineHCID 223354025-Bromo-1,2,3,4-tetrahydro-2-(phenylmethyl)-2,6-naphthyridineHCID 23676156Sodium t-butoxide

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178477754HCID 178477754, compoundCatalyst

Conditions

Temperature
160 °C

Procedure

The 2-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 1200 s 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 sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give a brown-purple residue. The residue was purified 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 sat. NaHCO3 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

Sources & evidence

ORD record
ord-11453f9b8d27497fad022fc2df6db6b9
Source dataset
uspto-grants-2008_08
Patent number
US07414131B2

Reaction notes

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