Citric Acid → HCID 10272047, compound

HRID 2222317Notes

Reaction equation

HRID 2222317 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C1N=CN([C:17]([N:19]2C=N[CH:21]=[CH:20]2)=[O:18])C=1.[Cl:24][C:25]1[CH:38]=[CH:37][C:28]([O:29][C:30]2[CH:36]=CC(N)=[CH:32][CH:31]=2)=[CH:27][CH:26]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:17]([NH:19][C:20]2[CH:21]=[CH:36][C:30]([O:29][C:28]3[CH:27]=[CH:26][C:25]([Cl:24])=[CH:38][CH:37]=3)=[CH:31][CH:32]=2)=[O:18])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 75784-(4-Chlorophenoxy)anilineHCID 682631,1'-CarbonyldiimidazoleHCID 123519414-(tert-Butyl)pyridin-2-amine

Product 1

HCID 10272047HCID 10272047, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-tert-butyl-2-aminopyridine (0.177 g, 1.18 mmol, 1 equiv.) in 1.2 mL of anh. CH2Cl2 (1.2 mL) was added to CDI (0.200 g, 1.24 mmol, 1.05 equiv) and the mixture was allowed to stir under argon at room temperature 1 d. To the resulting solution was added 4-(4-chlorophenoxy)aniline (0.259 g, 1.18 mmol, 1 equiv.) in one portion. The resulting mixture was stirred at room temperature for 1 d, then was treated with a 10% citric acid solution (2 mL) and allowed to stir for 1 h. The resulting organic layer was extracted with EtOAc (3×5 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The resultant residue was treated with CH2Cl2 (10 mL) and a 1 N aqueous NaOH solution. This mixture was allowed to stir overnight. The resulting organic layer was extracted with CH2Cl2 (3×5 mL). The combined organic layers were (MgSO4) and concentrated in vacuo. The resultant solids were suspended in diethyl ether (10 mL) and sonicated for 15 minutes. The resulting white solids were dried to give N-(4-tert-butylpyridyl)-N′-(4-(4-chlorophenoxy)phenyl) urea (42 mg, 9%): mp 198-199° C. B3. Reaction of Substituted Aniline with N,N′-Carbonyldiimidazole Followed by Reaction with a Heterocyclic Amine

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1 d
  2. stirringto stir for 1 h
  3. extractionThe resulting organic layer was extracted with EtOAc (3×5 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. additionThe resultant residue was treated with CH2Cl2 (10 mL)
  7. stirringto stir overnight
  8. extractionThe resulting organic layer was extracted with CH2Cl2 (3×5 mL)
  9. concentrationconcentrated in vacuo
  10. customsonicated for 15 minutes
  11. customThe resulting white solids were dried

Sources & evidence

ORD record
ord-f4f8327cb4f04df3b3a98c07eafd0113
Source dataset
uspto-grants-2008_05
Patent number
US07371763B2

Reaction notes

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