1-Hydroxybenzotriazole → 2-[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-Methylacetamide

HRID 1188995노트

반응식

HRID 1188995 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([OH:20])=O)[CH2:15][N:16]=1)=[CH:8]2.Cl.[CH2:33]([N:35]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.CN>O.C(N(CC)CC)C.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([NH:35][CH3:33])=[O:20])[CH2:15][N:16]=1)=[CH:8]2

참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 67118501[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

생성물 1

HCID 445165552-[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-Methylacetamide수율 67%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

실험 절차

A mixture of [2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (800 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (500 mg), 1-hydroxybenzotriazole (350 mg) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 30 min. Then triethylamine (440 mg) and methylamine hydrochloride (230 mg) were added to the mixture. The whole was stirred at room temperature for 20-h. Water was added to the mixture and the resultant was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 95:5, volume ratio) to give pale yellow crystals. The crystals were washed with ethyl acetate-hexane to give the title compound (540 mg, 67%) as pale yellow crystals. The crystals were recrystallized from acetone-hexane to give colorless prisms. MS 475 (MH+). mp 201-202° C.

후처리

  1. extractionthe resultant was extracted with ethyl acetate
  2. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 95:5, volume ratio)
  7. customto give pale yellow crystals
  8. washThe crystals were washed with ethyl acetate-hexane

출처 및 근거

ORD 기록
ord-33f838f082a94c3da96465f2fd442f1d
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673942B2

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