Ammonia → 2-(Ethyl-methyl-amino)-6-methyl-isonicotinonitrile

HRID 2047282Notes

Reaction equation

HRID 2047282 reaction equation
[CH2:1]([N:3]([CH3:14])[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:7](O)=O)[CH3:2].CC[N:17](C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.N.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>CN(C=O)C.O1CCOCC1.C(Cl)Cl>[CH2:1]([N:3]([CH3:14])[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:7]#[N:17])[CH3:2]

Participants

10

Reactant 6

HCID 222AmmoniaHCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 584180642-(Ethyl-methyl-amino)-6-methyl-isonicotinic acid

Product 1

HCID 685793492-(Ethyl-methyl-amino)-6-methyl-isonicotinonitrileYield 16.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(ethyl-methyl-amino)-6-methyl-isonicotinic acid (2.03 g, 8.80 mmol) and DIPEA (3.41 g, 26.4 mmol) in DMF (80 mL) is added PyBOP (5.00 g, 9.61 mmol) at 0° C. The mixture is stirred for 15 min before 0.5 M NH3 in dioxane (52 mL) is added. Stirring is continued at rt for 2 h before the mixture is again cooled to 0° C. Pyridine (4.35 g, 44.8 mmol) followed by trifluoroacetic anhydride (9.29 g, 44.2 mmol) is carefully added and the reaction mixture is stirred for 2 h while warming to rt. The mixture is then stirred at 70° C. for 15 h, cooled to rt, diluted with DCM and washed with 10% aq. citric acid solution followed by sat. aq. Na2CO3-solution. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-(ethyl-methyl-amino)-6-methyl-isonicotinonitrile (257 mg) as a pale yellow oil; LC-MS: tR=0.58 min, [M+1]+=176.09.

Workup

  1. additionis added
  2. additionis carefully added
  3. stirringthe reaction mixture is stirred for 2 h
  4. temperaturewhile warming to rt
  5. stirringThe mixture is then stirred at 70° C. for 15 h
  6. temperaturecooled to rt
  7. washwashed with 10% aq. citric acid solution
  8. extractionextract
  9. dry with materialis dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1

Sources & evidence

ORD record
ord-3d52c09c47ad4ed09e3aecf39208b888
Source dataset
uspto-grants-2013_11
Patent number
US08592460B2

Reaction notes

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