Pyridine → HCID 15405474, compound

HRID 2120286Notes

Reaction equation

HRID 2120286 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:15]2[CH2:16][C@H:11]([CH2:12][CH2:13][C@@H:14]2[N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][CH:20]=[N:21][C:22]=3[NH2:26])[CH2:10][C:9]1=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[CH3:34][O:35][C:36]1[CH:44]=[CH:43][C:39]([C:40](Cl)=[O:41])=[CH:38][CH:37]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@H:15]2[CH2:16][C@H:11]([CH2:12][CH2:13][C@@H:14]2[N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][CH:20]=[N:21][C:22]=3[NH:26][C:40](=[O:41])[C:39]2[CH:43]=[CH:44][C:36]([O:35][CH3:34])=[CH:37][CH:38]=2)[CH2:10][C:9]1=[O:27])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 1049PyridineHCID 7477p-Anisoyl chlorideHCID 86759330HCID 86759330, compound

Product 1

HCID 15405474HCID 15405474, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100 ml two-necked round-bottomed flask was loaded with 4.96 g of Boc-A lactams [sic] 15e (13.3 mmol) and 60 ml of dry CH2Cl2. 5.35 ml of dry pyridine (66.5 mmol) were then added, followed by 1.59 g of DMAP (1.3 mmol). After cooling to 0° C., 5.4 ml of 4-methoxybenzoyl chloride (39.9 mmol) were added dropwise and the mixture was stirred at 0° C. for 15 min. The ice bath was removed and the reaction mixture was stirred at room temperature for 22 h. The reaction mixture was then again cooled to 0° C. and 35 ml of MeOH were added dropwise. After 30 min at 0° C., 80 ml of a saturated solution of NH3 in MeOH were added dropwise. A white precipitate was formed, which dissolved after complete addition of the solution. After 30 min, the ice bath was removed and the reaction was stirred at room temperature for a further 2 h. The solvent was then removed under reduced pressure and the resulting residue was dissolved in 200 ml of CH2Cl2. The solution was washed successively with 150 ml of saturated NaHCO3 solution and aqueous citric acid solution (20%, 2×100 ml), washed [sic] over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by means of chromatography (5.2×18 cm silica gel; eluent: EtOAc/MeOH 40:3) to afford 5.93 g of 15f (88%).

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 22 h
  3. temperatureThe reaction mixture was then again cooled to 0° C.
  4. addition35 ml of MeOH were added dropwise
  5. waitAfter 30 min at 0° C.
  6. addition80 ml of a saturated solution of NH3 in MeOH were added dropwise
  7. customA white precipitate was formed
  8. dissolutionwhich dissolved
  9. additionafter complete addition of the solution
  10. waitAfter 30 min
  11. customthe ice bath was removed
  12. stirringthe reaction was stirred at room temperature for a further 2 h
  13. customThe solvent was then removed under reduced pressure
  14. dissolutionthe resulting residue was dissolved in 200 ml of CH2Cl2
  15. washThe solution was washed successively with 150 ml of saturated NaHCO3 solution and aqueous citric acid solution (20%, 2×100 ml)
  16. washwashed [sic] over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo
  19. customThe resulting residue was purified by means of chromatography (5.2×18 cm silica gel; eluent: EtOAc/MeOH 40:3)

Sources & evidence

ORD record
ord-6d3f650089694c17aed3a9b4bd6c4282
Source dataset
uspto-grants-2004_02
Patent number
US06689884B1

Reaction notes

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