N,N-Dimethylaniline → HCID 71503460, compound

HRID 525991Notes

Reaction equation

HRID 525991 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][CH:3]=1.CN(C)C1C=CC=CC=1.[CH3:19][O:20][C:21](=[O:27])[CH2:22][CH2:23][C:24](Cl)=[O:25]>O1CCCC1>[C:8]([C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:24](=[O:25])[CH2:23][CH2:22][C:21]([O:20][CH3:19])=[O:27])=[N:7][CH:6]=1)#[N:9]

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 8182602-Amino-5-cyanopyridine

Product 1

HCID 71503460HCID 71503460, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 6-amino-3-pyridinecarbonitrile (commercially available, 0.470 g, 1.0 eq.) was dissolved in tetrahydrofuran (10 mL) then N,N-dimethylaniline (0.5 mL, 1.0 eq.) and methyl-4-chloro-4-oxo-butanoate (0.54 mL, 1.1 eq.) were successively added. The mixture was reflux for 12 h. The reaction was stopped and the solution was partitioned between ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layer was dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography eluting with cyclohexane-ethyl acetate to give methyl 4-[(5-cyano-2-pyridyl)amino]-4-oxo-butanoate A1 (71%). M.p.=161-164° C. 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.20 (m, 2H), 3.58 (s, 3H), 2.74 (t, 2H), 2.61 (t, 2H) ppm. LC-MS (Method B): RT 1.19, 234 (M+H+) The following compounds from table A or B were prepared by the same method using commercial or described starting aminopyridine:

Workup

  1. temperatureThe mixture was reflux for 12 h
  2. customthe solution was partitioned between ethyl acetate and water
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×)
  5. customThe combined organic layer was dried on magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash chromatography
  8. washeluting with cyclohexane-ethyl acetate

Sources & evidence

ORD record
ord-b47d5a222ef048178d1a733385bf5618
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

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