Nitrogen → HCID 18516454, compound

HRID 1597475Notes

Reaction equation

HRID 1597475 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](O)([C:33]2[N:34]([CH3:38])[CH:35]=[N:36][CH:37]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH:13]=[C:12]3[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH:22]=2)=[CH:4][CH:3]=1.N#N.C(=O)([O-])[O-].[K+].[K+].[NH:48]1[CH:52]=[N:51][CH:50]=[N:49]1>S(Cl)(Cl)=O.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:33]2[N:34]([CH3:38])[CH:35]=[N:36][CH:37]=2)([N:48]2[CH:52]=[N:51][CH:50]=[N:49]2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH:13]=[C:12]3[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]#[C:28][C:29]([CH3:31])([CH3:32])[CH3:30])[CH:22]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 185164526-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3,3-dimethyl-but-1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one

Product 1

HCID 18516454HCID 18516454, compoundYield 40.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

6-[(4chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3,3-dimethyl-but-1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one (330 mg, 0.633 mMol) was dissolved in 4 mL of thionyl chloride and stirred at ambient temperature under a stream of dry N2 for 2 hours. The reaction mixture was then concentrated under vacuum and toluene (5 mL) was added to the reaction mixture which was subsequently concentrated under vacuum to give a yellow solid. 210 mg of the yellow solid was dissolved in 5.0 mL of anhydrous DMF under an atmosphere of dry N2. To this solution was added 800 mg of potassium carbonate and 300 mg of 1,2,4-triazole and the reaction mixture was subsequently heated to 80° C. and stirred overnight at this temperature. The reaction mixture was then concentrated under vacuum and partitioned between EtOAc and water. The EtOAc layer was washed 3 more times with water and then with brine. The EtOAc layer was then dried over Na2SO4, filtered and concentrated under vacuum to give a yellow solid. The solid was chromatographed on flash silica gel eluting with a gradient of MeOH/DCM/NH4OH (2/98/0.1) to MeOH/DCM/NH4OH (7/93/0.1) to give 150 mg of the titled product as a white solid.

Workup

  1. concentrationThe reaction mixture was then concentrated under vacuum and toluene (5 mL)
  2. additionwas added to the reaction mixture which
  3. concentrationwas subsequently concentrated under vacuum
  4. customto give a yellow solid
  5. concentrationThe reaction mixture was then concentrated under vacuum
  6. custompartitioned between EtOAc and water
  7. washThe EtOAc layer was washed 3 more times with water
  8. dry with materialThe EtOAc layer was then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customto give a yellow solid
  12. customThe solid was chromatographed on flash silica gel eluting with a gradient of MeOH/DCM/NH4OH (2/98/0.1) to MeOH/DCM/NH4OH (7/93/0.1)

Sources & evidence

ORD record
ord-f2c86b74ee7646d3ac5231250278c537
Source dataset
uspto-grants-2001_09
Patent number
US06294552B1

Reaction notes

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