Pyridine → N-(2-(6,7-Dimethoxyquinolin-4-ylsulfanyl)thiazol-5-yl)-N'-(thiazol-2-yl)urea

HRID 853371Notes

Reaction equation

HRID 853371 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[S:15][C:16]1[S:17][C:18]([NH2:21])=[CH:19][N:20]=1.N1C=CC=CC=1.Cl[C:29](OC1C=CC([N+]([O-])=O)=CC=1)=[O:30].[NH2:41][C:42]1[S:43][CH:44]=[CH:45][N:46]=1>O1CCCC1.CO.C(OCC)(=O)C.O.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[S:15][C:16]1[S:17][C:18]([NH:21][C:29]([NH:41][C:42]2[S:43][CH:44]=[CH:45][N:46]=2)=[O:30])=[CH:19][N:20]=1

Participants

10

Reactant 4

HCID 1049PyridineHCID 21552-AminothiazoleHCID 821294-Nitrophenyl chloroformateHCID 229363012-(6,7-Dimethoxyquinolin-4-ylsulfanyl)thiazol-5-ylamine

Product 1

HCID 22936997N-(2-(6,7-Dimethoxyquinolin-4-ylsulfanyl)thiazol-5-yl)-N'-(thiazol-2-yl)ureaYield 19%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

After dissolving 2-(6,7-dimethoxyquinolin-4-ylsulfanyl)thiazol-5-ylamine (216 mg, 0.676 mmol) and pyridine (58.8 mg, 0.743 mmol) in tetrahydrofuran (3 ml), 4-nitrophenyl chloroformate (150 mg, 0.743 mmol) was added while cooling on ice, the mixture was stirred at room temperature for 30 minutes, 2-aminothiazole (101 mg, 1.01 mmol) and triethylamine (1 ml) were added, and the mixture was heated and stirred at 60° C. for 1 hour. The reaction solution was distributed between ethyl acetate and water, the organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was distilled off under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (eluent—ethyl acetate:methanol=30:1), and the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, after which the crystals were filtered out, washed with hexane and then blow-dried to obtain the title compound (57 mg, 0.128 mmol,. 19%) as colorless crystals.

Workup

  1. additionwas added
  2. temperaturewhile cooling on ice
  3. temperaturethe mixture was heated
  4. stirringstirred at 60° C. for 1 hour
  5. washthe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationthe drying agent was filtered off
  8. distillationthe filtrate was distilled off under reduced pressure
  9. customThe obtained crude product
  10. additionthe fraction containing the target substance
  11. concentrationwas concentrated
  12. additiondiluted with hexane
  13. filtrationafter which the crystals were filtered out
  14. washwashed with hexane
  15. customblow-dried

Sources & evidence

ORD record
ord-0aa5619d0a904859821dc708be66166e
Source dataset
uspto-grants-2007_08
Patent number
US07253286B2

Reaction notes

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