Picolinic acid → Pyridine-2-carboxylic acid-(4-(1-acetyl-pyrrolidin-2-yl)-3-fluoro-phenyl)-amide

HRID 13355

Reaction equation

HRID 13355 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.Cl.[CH3:11]N(C)CCCN=C=NCC.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:33][CH2:32][CH2:31][N:30]2[C:34](OC(C)(C)C)=[O:35])=[C:25]([F:41])[CH:24]=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.N1C=CC=CC=1>[C:34]([N:30]1[CH2:31][CH2:32][CH2:33][CH:29]1[C:26]1[CH:27]=[CH:28][C:23]([NH:22][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[O:9])=[CH:24][C:25]=1[F:41])(=[O:35])[CH3:11]

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23145592t-Butyl 2-(4-amino-2-fluoro-phenyl)-pyrrolidine-1-carboxylate

Product 1

HCID 23145364Pyridine-2-carboxylic acid-(4-(1-acetyl-pyrrolidin-2-yl)-3-fluoro-phenyl)-amide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6212ChloroformSolvent3×

Procedure

90 mg of pyridine-2-carboxylic acid and 190 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride were added in order to a pyridine (2 ml) solution of 181 mg of t-butyl 2-(4-amino-2-fluoro-phenyl)-pyrrolidine-1-carboxylate, and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid was diluted with chloroform, washed with water and saturated saline, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and 2 ml of 4 N hydrochloric acid-dioxane solution was added to 300 mg of the resulting residue, and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with chloroform, and made basic with aqueous saturated sodium bicarbonate solution added thereto, and the organic layer was washed with saturated saline and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and 0.020 ml of acetic anhydride was added to a pyridine (1 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 20 minutes. The reaction liquid was diluted with chloroform, washed with water and saturated saline in order, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=50/1) to obtain the entitled compound as a yellow solid.

Workup

  1. customthe reaction liquid
  2. customThe reaction liquid
  3. washwashed with water and saturated saline
  4. dry with materialdried with anhydrous magnesium sulfate
  5. customThe solvent was evaporated away under reduced pressure, and 2 ml of 4 N hydrochloric acid-dioxane solution
  6. additionwas added to 300 mg of the resulting residue
  7. customthe reaction liquid
  8. stirringwas stirred at room temperature for 1 hour
  9. customThe reaction liquid
  10. additionadded
  11. washthe organic layer was washed with saturated saline
  12. dry with materialdried with anhydrous magnesium sulfate
  13. customThe solvent was evaporated away under reduced pressure, and 0.020 ml of acetic anhydride
  14. additionwas added to a pyridine (1 ml) solution of the resulting residue
  15. customthe reaction liquid
  16. stirringwas stirred at room temperature for 20 minutes
  17. customThe reaction liquid
  18. washwashed with water and saturated saline in order
  19. dry with materialdried with anhydrous magnesium sulfate
  20. customThe solvent was evaporated away under reduced pressure
  21. customthe resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=50/1)

Sources & evidence

ORD record
ord-0b7e429ae81b453c8d805025d655020c
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Linked notes

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