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

HRID 1246728Notes

Reaction equation

HRID 1246728 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[CH2:12][CH:11]=[C:10]([C:13]([OH:15])=O)[CH2:9][CH2:8]1.C(Cl)(C(Cl)=O)=O.N1C=CC=CC=1.[C:28]([C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1)([CH3:31])([CH3:30])[CH3:29]>C(Cl)Cl.C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.O.CN(C=O)C>[C:28]([C:32]1[CH:33]=[CH:34][C:35]([NH:36][C:13]([C:10]2[CH2:9][CH2:8][N:7]([C:2]3[N:1]=[CH:6][CH:5]=[CH:4][N:3]=3)[CH2:12][CH:11]=2)=[O:15])=[CH:37][CH:38]=1)([CH3:31])([CH3:29])[CH3:30]

Participants

10

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 698614-Tert-ButylanilineHCID 219047301-Pyrimidin-2-yl-1,2,3,6-tetrahydropyridine-4-carboxylic acid

Product 1

HCID 44580004N-(4-tert-Butylphenyl)-1-(pyrimidin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamideYield 534.8%

Reagents, catalysts & solvents 5

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

Procedure

To a suspension of 1-Pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (60.4 mg, 0.194 mmol) and DMF (cat) in CH2Cl2 (1 mL) was added (COCl)2 (0.027 mL, 0.31 mmol). The mixture was stirred for 90 minutes, diluted with PhMe (0.5 mL), concentrated under reduced pressure to dryness, and dissolved in CH2Cl2 (1.5 mL). To the solution were added pyridine (0.027 mL, 0.33 mmol), DMAP (cat), and 4-tert-butylaniline (0.037 mL, 0.023 mmol). The mixture was stirred 1 hour, diluted with water and extracted with CH2Cl2, dried (Na2SO4), and purified by flash chromatography (7% EtOAc/CH2Cl2) to provide 1-Pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-tert-butyl-phenyl)-amide as a white solid (54.2 mg, 0.123 mmol, 63%): MS (ESI+) m/z 337 (M+H)+, m/z 334 (M−H)−; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.31 (s, 9 H), 2.59 (m, 2 H), 4.04 (t, J=5.6 Hz, 2 H), 4.44 (q, J=3.1 Hz, 2 H), 6.54 (t, J=4.7 Hz, 1 H), 6.75 (m, 1 H), 7.36 (m, 3 H), 7.47 (m, 2 H), 8.35 (d, J=4.7 Hz, 2 H).

Workup

  1. concentrationconcentrated under reduced pressure to dryness
  2. dissolutiondissolved in CH2Cl2 (1.5 mL)
  3. stirringThe mixture was stirred 1 hour
  4. extractionextracted with CH2Cl2
  5. dry with materialdried (Na2SO4)
  6. custompurified by flash chromatography (7% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-832cb8baa5f742c599e05cef6d7cd5c7
Source dataset
uspto-grants-2006_10
Patent number
US07129235B2

Reaction notes

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