Carbamate → HCID 67439726, compound

HRID 1665827Notes

Reaction equation

HRID 1665827 reaction equation
C(=O)([O-])N.[NH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[H-].[Na+].F[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[C:6]1([N:5]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:15]2[NH2:16])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

7

Reactant 5

HCID 276CarbamateHCID 6115AnilineHCID 97462-FluoropyridineHCID 24758Sodium hydrideHCID 516892Sodium Bicarbonate

Product 1

HCID 67439726HCID 67439726, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A substituted aniline was N-protected with a formyl, Boc or similar amide or carbamate protecting group using a standard method. Subsequently, this N-protected aniline derivative was dissolved in DMF (under N2), cooled to 0° C. and added NaH (1.1 eq). After stirring for 30 min at rt, 2-fluoropyridine was added to the reaction mixture and stirring was continued at 70° C. for 1-3 days. After cooling to rt, aqueous saturated NaHCO3 was added and the mixture extracted with EtOAc. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo to give the crude product which was purified by preparative LC-MS or by column chromatography to give the desired N-protected N-phenyl-2-aminopyridine. After a reaction step to remove the N-protecting group, using a standard method, the obtained phenyl-pyridin-2-yl-amine was dissolved in acetonitrile (under N2) in a closed vial and added the required halide for the N-alkylation. The reaction mixture was then heated to 100-150° C. for 30-720 min using MW irradiation. After cooling to rt, the crude product could be isolated upon aqueous basic work-up and subsequently purified by preparative LC-MS or, alternatively, by column chromatography and/or recrystallization to give the desired N,N′-disubstituted 2-aminopyridine.

Workup

  1. stirringstirring
  2. waitwas continued at 70° C. for 1-3 days
  3. temperatureAfter cooling to rt
  4. extractionthe mixture extracted with EtOAc
  5. dry with materialThe combined organic phases were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product which
  9. customwas purified by preparative LC-MS or by column chromatography

Sources & evidence

ORD record
ord-554b566d1ee74e368b1e99ceea5be7f2
Source dataset
uspto-grants-2011_10
Patent number
US08039632B2

Reaction notes

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