Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoate → Methyl 4-chloro-3-{[(3,5-dimethylpyrazin-2-yl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoate

HRID 1399100Notes

Reaction equation

HRID 1399100 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:26]([CH3:27])=[N:25][C:24]([CH3:28])=[CH:23][N:22]=1)=[C:19]=[S:20]>O1CCCC1>[Cl:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[C:3]([NH:13][CH2:14][CH2:15][CH2:16][OH:17])[C:2]=1[NH:1][C:19](=[S:20])[NH:18][C:21]1[C:26]([CH3:27])=[N:25][C:24]([CH3:28])=[CH:23][N:22]=1

Participants

4

Reactant 2

HCID 68739849Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoateHCID 866328962-Isothiocyanato-3,5-dimethylpyrazine

Product 1

HCID 86632931Methyl 4-chloro-3-{[(3,5-dimethylpyrazin-2-yl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoateYield 52.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 3-amino-4-chloro-2-[(3-hydroxypropyl)amino]benzoate (500 mg, 1.94 mmol) and 2-isothiocyanato-3,5-dimethylpyrazine (866 mg, 5.24 mmol) in tetrahydrofuran (4.0 mL) was stirred at 60° C. for 6 hr. The mixture was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give methyl 4-chloro-3-{[(3,5-dimethylpyrazin-2-yl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoate as a yellow solid (430 mg).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture
  3. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-2ac7e165e0454a36b440f921b5e15614
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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