Methanol → 4-Amino-3-pyridinecarboxamide

HRID 1767048Notes

Reaction equation

HRID 1767048 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:14]([C:15]([OH:17])=O)=[CH:13][N:12]=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(C1NC=CN=1)(C1[NH:21]C=CN=1)=O.C(Cl)Cl.CO>CN(C=O)C>[NH2:8][C:9]1[C:14]([C:15]([NH2:21])=[O:17])=[CH:13][N:12]=[CH:11][CH:10]=1.[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[CH:10]=[CH:11][N:12]=[CH:13][C:14]=1[C:15](=[O:17])[NH2:21])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 221726234-{[(Tert-butoxy)carbonyl]amino}pyridine-3-carboxylic acid

Product 2

HCID 134980824-Amino-3-pyridinecarboxamideHCID 58889972(3-Carbamoyl-pyridin-4-yl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

4-tert-Butoxycarbonylamino-nicotinic acid (1.0 g, 4.20 mmol) was suspended in dry DMF (50 mL) followed by carbonyl-diimidazole (CDI, 1.36 g, 8.40 mmol). The mixture was heated to 60° C. for 1 h, then cooled. Dry ammonia gas was slowly bubbled through this solution for 1 h, followed by evaporation of the mixture. The residue was dissolved in water (20 mL)/chloroform (50 mL) and shaken then the layers separated. The aqueous layer was extracted further with chloroform (3×50 mL) and the combined organic extracts dried (MgSO4) and evaporated to give a yellow oily solid. Silica gel chromatography (CH2Cl2, 0–15% MeOH gradient) gave the desired product, (3-Carbamoyl-pyridin-4-yl)-carbamic acid tert-butyl ester, as a yellow solid. This material was directly treated with trifluoroacetic acid (TFA, 20 mL) stirred at r.t. for 45 min., then evaporated to give the desired amine, 4-Amino nicotinamide, as its TFA salt (892 mg, 85% yield over 2 steps).

Workup

  1. temperaturecooled
  2. customDry ammonia gas was slowly bubbled through this solution for 1 h
  3. customfollowed by evaporation of the mixture
  4. dissolutionThe residue was dissolved in water (20 mL)/chloroform (50 mL)
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted further with chloroform (3×50 mL)
  7. dry with materialthe combined organic extracts dried (MgSO4)
  8. customevaporated
  9. customto give a yellow oily solid

Sources & evidence

ORD record
ord-9b96046278e74dfebff55b0b36391a98
Source dataset
uspto-grants-2007_06
Patent number
US07232824B2

Reaction notes

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