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

HRID 1189025노트

반응식

HRID 1189025 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.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:54][CH2:55][C:56]([CH3:59])([OH:58])[CH3:57]>CN(C)C=O.O>[OH:58][C:56]([CH3:59])([CH3:57])[CH2:55][NH:54][C:18](=[O:20])[CH2:17][CH:14]1[S:13][C:12]([C:9]2[NH:10][C:11]3[C:7]([CH:8]=2)=[CH:6][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:4][C:3]=3[O:2][CH3:1])=[N:16][CH2:15]1

참가 물질

7

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 951022-Propanol, 1-amino-2-methyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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 44516879N-(2-Hydroxy-2-methylpropyl)-2-[2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamide수율 65%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

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 (200 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (120 mg), 1-hydroxybenzotriazole (90 mg) and N,N-dimethylformamide (3 mL) was stirred at room temperature for 30 min. A solution of 1-amino-2-methylpropan-2-ol (77 mg) in N,N-dimethylformamide (1 mL) was added to the mixture. The whole was stirred at room temperature for 15 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 colorless crystals. The crystals were recrystallized from acetone-hexane to give the title compound (150 mg, 65%) as colorless prisms. MS 533 (Me). mp 200-201° C.

후처리

  1. stirringThe whole was stirred at room temperature for 15 h
  2. extractionthe resultant was extracted with ethyl acetate
  3. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 95:5, volume ratio)
  8. customto give colorless crystals
  9. customThe crystals were recrystallized from acetone-hexane

출처 및 근거

ORD 기록
ord-e31238e0645e458f92c6aab05f87999e
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673942B2

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