Sodium Hydroxide → N4-(4-{4-[(Anilinocarbonyl)amino]-3-chlorophenoxy}-2-pyridyl)-1-methyl-4-piperidinecarboxamide

HRID 1010197Notes

Reaction equation

HRID 1010197 reaction equation
[NH:1]([C:8]([NH:10][C:11]1[CH:39]=[CH:38][C:14]([O:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]([CH:25]3[CH2:30][CH2:29][N:28]([C:31](OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[O:24])[CH:17]=2)=[CH:13][C:12]=1[Cl:40])=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C(=O)(O)[O-].[Na+].[OH-].[Na+]>FC(F)(F)C(O)=O>[NH:1]([C:8]([NH:10][C:11]1[CH:39]=[CH:38][C:14]([O:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]([CH:25]3[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]3)=[O:24])[CH:17]=2)=[CH:13][C:12]=1[Cl:40])=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 58931346t-Butyl4-{[(4-{4-[(anilinocarbonyl)amino]-3-chlorophenoxy}-2-pyridyl)amino]carbonyl}-1-piperidinecarboxylateHCID 86585896Sodium bicarbonate water

Product 1

HCID 58931464N4-(4-{4-[(Anilinocarbonyl)amino]-3-chlorophenoxy}-2-pyridyl)-1-methyl-4-piperidinecarboxamideYield 78.6%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

After dissolving 120 mg of t-butyl 4-{[(4-{4-[(anilinocarbonyl)amino]-3-chlorophenoxy}-2-pyridyl)amino]carbonyl}-1-piperidine carboxylate in 5 ml of trifluoroacetic acid, the solution was stirred at room temperature for 5 minutes. Sodium bicarbonate water and 5N aqueous sodium hydroxide were added and extraction was performed with ethyl acetate. The extract was washed with brine and dried over sodium sulfate. The drying agent was filtered off, and the solvent was distilled off under reduced pressure. After adding 5 ml of tetrahydrofuran, 26 mg of acetic acid, 92 mg of sodium triacetoxyborohydride and 0.5 ml of formaldehyde (37% in water) to the residue, the mixture was stirred at room temperature for 10 minutes. Sodium bicarbonate water and 5N aqueous sodium hydroxide were added to the reaction solution, and extraction was performed with ethyl acetate. The extract was washed with brine and then passed through a glass filter coated with NH type silica gel. The silica gel was washed thoroughly with ethyl acetate, the ethyl acetate layers were combined and subjected to distillation under reduced pressure, and the residue was solidified with ethyl acetate and hexane to obtain 80 mg of a colorless powder.

Workup

  1. extractionextraction
  2. washThe extract was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationThe drying agent was filtered off
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionAfter adding 5 ml of tetrahydrofuran, 26 mg of acetic acid, 92 mg of sodium triacetoxyborohydride and 0.5 ml of formaldehyde (37% in water) to the residue
  7. stirringthe mixture was stirred at room temperature for 10 minutes
  8. additionSodium bicarbonate water and 5N aqueous sodium hydroxide were added to the reaction solution, and extraction
  9. washThe extract was washed with brine
  10. filtrationfilter
  11. washThe silica gel was washed thoroughly with ethyl acetate
  12. distillationsubjected to distillation under reduced pressure

Sources & evidence

ORD record
ord-70f0a95e3d2a4cd0a90d719637641fa6
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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