Thiourea → HCID 68760757, compound

HRID 1628525Notes

Reaction equation

HRID 1628525 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].[N:18]([C:21]1[C:22]([CH3:29])=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)=[C:19]=S.NC(N)=S>O1CCCC1>[Cl:12][C:11]1[C:2]2[N:1]=[C:19]([NH:18][C:21]3[C:22]([CH3:29])=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=3)[N:13]([CH2:14][CH2:15][CH2:16][OH:17])[C:3]=2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 2723790ThioureaHCID 68739849Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoateHCID 86632901HCID 86632901, compound2×

Product 1

HCID 68760757HCID 68760757, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 3-amino-4-chloro-2-[(3-hydroxypropyl)amino]benzoate (2.00 g) in tetrahydrofuran (40.0 mL) was added 3-isothiocyanato-6-methoxy-2-methylpyridine (1.67 g, 9.277 mmol). The reaction mixture was stirred at 70° C. for 14 hrs. The starting material wasn't consumed completely. To the mixture was added 3-isothiocyanato-6-methoxy-2-methylpyridine (1.67 g, 9.277 mmol). The reaction mixture was stirred at 70° C. for 36 hrs. After cooling, the solvent was removed by concentration. The residue was purified by silica gel column chromatography eluting with a 30-80% ethyl acetate/n-hexane gradient mixture to give the mixture contained thiourea and title compound. The mixture was subject to next step without further purification. The mixture was dissolved into tetrahydrofuran (30 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (885.7 mg, 4.62 mmol) and triethylamine (0.71 mL, 5.08 mmol). The reaction mixture was stirred at 50° C. for 2 hrs. After cooling, the mixture was diluted with water, 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 to give the title compound as a colorless solid (1.50 g, 3.72 mmol, 48% (2 steps)).

Workup

  1. customThe starting material wasn't consumed completely
  2. stirringThe reaction mixture was stirred at 70° C. for 36 hrs
  3. temperatureAfter cooling
  4. customthe solvent was removed by concentration
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with a 30-80% ethyl acetate/n-hexane gradient mixture
  7. customto give the mixture

Sources & evidence

ORD record
ord-5daccf8d8cf3447a8a4562eb4047e885
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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