Water → methyl 2-[(2,4-dichloro-6-methylphenyl)amino]-1-(2-hydroxyethyl)-1H-benzimidazole-7-carboxylate

HRID 1628941노트

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HRID 1628941 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH:10][C:11]([NH:13][C:14]1[C:15]([NH:24][CH2:25][CH2:26][OH:27])=[C:16]([CH:21]=[CH:22][CH:23]=1)[C:17]([O:19][CH3:20])=[O:18])=S.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.O>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH:10][C:11]1[N:24]([CH2:25][CH2:26][OH:27])[C:15]2[C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:21][CH:22]=[CH:23][C:14]=2[N:13]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86632915Methyl 3-{[(2,4-dichloro-6-methylphenyl)carbamothioyl]amino}-2-[(2-hydroxyethyl)amino]benzoate

생성물 1

HCID 68772933methyl 2-[(2,4-dichloro-6-methylphenyl)amino]-1-(2-hydroxyethyl)-1H-benzimidazole-7-carboxylate수율 76%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

To a solution of methyl 3-{[(2,4-dichloro-6-methylphenyl)carbamothioyl]amino}-2-[(2-hydroxyethyl)amino]benzoate (300 mg, 0.70 mmol) in tetrahydrofuran (7.0 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (148 mg, 0.77 mmol) and triethylamine (0.108 mL, 0.77 mmol) at room temperature. The mixture was stirred at 50° C. for 14 hr. Water was added to the reaction mixture at room temperature and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give methyl 2-[(2,4-dichloro-6-methylphenyl)amino]-1-(2-hydroxyethyl)-1H-benzimidazole-7-carboxylate (210 mg, 0.53 mmol, 76%) as a pale yellow solid. To a solution of methyl 2-[(2,4-dichloro-6-methylphenyl)amino]-1-(2-hydroxyethyl)-1H-benzimidazole-7-carboxylate (200 mg, 0.507 mmol) and triethylamine (0.28 mL, 3.8 mmol) was added methanesulfonyl chloride (0.079 mL, 1.02 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hr and at room temperature for 14 hr. Then the mixture was warmed to 45° C. and stirred at 45° C. for 8 hr. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 25-70% ethyl acetate/n-hexane gradient mixture to give the title compound (170 mg, 0.45 mmol, 89%) as colorless crystals.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-367f77fa2b934437a6ded725660ce592
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785460B2

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