Triethylamine → HCID 68763449, compound

HRID 1628524Notes

Reaction equation

HRID 1628524 reaction equation
[NH2:1][C:2]1[C:3]([NH:13][CH2:14][CH2:15][CH2:16][OH:17])=[C:4]([CH:9]=[CH:10][C:11]=1[Cl:12])[C:5]([O:7][CH3:8])=[O:6].[Br:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=S)=[C:21]([Cl:28])[CH:20]=1.NC(N)=S.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>O1CCCC1.C(=O)([O-])O.[Na+]>[Br:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]2[N:13]([CH2:14][CH2:15][CH2:16][OH:17])[C:3]3[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[C:11]([Cl:12])[C:2]=3[N:1]=2)=[C:21]([Cl:28])[CH:20]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 2723790ThioureaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2735551HCID 2735551, compound2×HCID 68739849Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoate

Product 1

HCID 68763449HCID 68763449, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of methyl 3-amino-4-chloro-2-[(3-hydroxypropyl)amino]benzoate (7.67 g, 29.72 mmol) in tetrahydrofuran (200 mL) was added 4-bromo-2-chloro-1-isothiocyanatobenzene (8.86 g, 35.66 mmol). The reaction mixture was stirred at room temperature for 2.5 d. The starting material wasn't consumed completely. To the mixture was added 4-bromo-2-chloro-1-isothiocyanatobenzene (1.47 g, 5.91 mmol). The reaction mixture was stirred at room temperature for 5 hrs. The solvent was removed by concentration. The residue was washed with diisopropyl ether to give a mixture contained the thiourea. The mixture was subject to next step without further purification. The mixture was dissolved into tetrahydrofuran (200 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (4.41 g, 22.97 mmol) and triethylamine (3.50 mL, 25.27 mmol). The reaction mixture was stirred at 50° C. for 13 hrs. After cooling, the mixture was diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was washed with diisopropyl ether/ethyl acetate to give the title compound as a colorless solid (9.08 g, 19.19 mmol, 65% (2 steps)).

Workup

  1. customThe starting material wasn't consumed completely
  2. stirringThe reaction mixture was stirred at room temperature for 5 hrs
  3. customThe solvent was removed by concentration
  4. washThe residue was washed with diisopropyl ether
  5. customto give a mixture
  6. customThe mixture was subject to next step without further purification
  7. dissolutionThe mixture was dissolved into tetrahydrofuran (200 mL)
  8. stirringThe reaction mixture was stirred at 50° C. for 13 hrs
  9. temperatureAfter cooling
  10. extractionextracted with ethyl acetate (×3)
  11. washThe combined organic layer was washed with brine (×1)
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. washThe residue was washed with diisopropyl ether/ethyl acetate

Sources & evidence

ORD record
ord-bd29652ed06642fb9dc789516774a9f2
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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