Pyridine → N-(4-tert-Butylphenyl)-1-(3-(trifluoromethyl)pyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide

HRID 1246723Notes

Reaction equation

HRID 1246723 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[C:4]([N:9]2[CH2:14][CH:13]=[C:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]2)=[N:5][CH:6]=[CH:7][CH:8]=1.C(Cl)(C(Cl)=O)=O.N1C=CC=CC=1.[C:32]([C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1)([CH3:35])([CH3:34])[CH3:33]>C(Cl)Cl.C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.O.CN(C=O)C>[C:32]([C:36]1[CH:37]=[CH:38][C:39]([NH:40][C:15]([C:12]2[CH2:11][CH2:10][N:9]([C:4]3[C:3]([C:2]([F:1])([F:19])[F:18])=[CH:8][CH:7]=[CH:6][N:5]=3)[CH2:14][CH:13]=2)=[O:17])=[CH:41][CH:42]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

10

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 698614-Tert-ButylanilineHCID 21904722HCID 21904722, compound

Product 1

HCID 11407011N-(4-tert-Butylphenyl)-1-(3-(trifluoromethyl)pyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

3′-(Trifluoromethyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxylic acid (0.300 g, 1.10 mmol) and a catalytic amount of DMF were combined in CH2Cl2 (4.0 mL) and treated with (COCl)2 (0.14 mL, 1.6 mmol). The mixture was stirred for 90 minutes, diluted with toluene (0.5 mL) and concentrated to dryness. The residue was dissolved in CH2Cl2 (4.0 mL) treated with pyridine (0.14 mL, 1.7 mmol), a catalytic amount of DMAP, and 4-tert-butylaniline (0.21 mL, 1.3 mmol). After 1 hour, the mixture was diluted with water and extracted with CH2Cl2. The organic phase was dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (2.5% ethyl acetate/CH2Cl2) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ 8.42 (dd, 1H), 7.89 (dd, 1H), 7.47 (d, 3H), 6.98 (dd, 1H), 6.76 (s, 1H), 4.06 (q, 2H), 3.53 (t, 2H), 2.67 (m, 2H); MS (m/z) 404.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in CH2Cl2 (4.0 mL)
  3. waitAfter 1 hour
  4. extractionextracted with CH2Cl2
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (2.5% ethyl acetate/CH2Cl2)

Sources & evidence

ORD record
ord-b25e0cfbe1244753aa56bb7026b73529
Source dataset
uspto-grants-2006_10
Patent number
US07129235B2

Reaction notes

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