1-Hydroxybenzotriazole → 2-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}-N-methylacetamide

HRID 1042153노트

반응식

HRID 1042153 반응식
[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:19]=2)[NH:16][C:15]([C:27]2[S:28][CH:29]([CH2:32][C:33]([OH:35])=O)[CH2:30][N:31]=2)=[CH:14]3)=[CH:6][CH:5]=1.Cl.[CH3:37][N:38](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.CN>CCCCCC.C(OCC)(=O)C.CO.O.CN(C)C=O.C(N(CC)CC)C>[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:19]=2)[NH:16][C:15]([C:27]2[S:28][CH:29]([CH2:32][C:33]([NH:38][CH3:37])=[O:35])[CH2:30][N:31]=2)=[CH:14]3)=[CH:6][CH:5]=1

참가 물질

11

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 66726112{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid

생성물 1

HCID 667259322-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}-N-methylacetamide수율 49%

시약·촉매·용매 6

HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8058Hexane용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of {2-[5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (300 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (231 mg), 1-hydroxybenzotriazole (162 mg), methylamine hydrochloride (81 mg), triethylamine (0.2 mL), and N,N-dimethylformamide (15 mL) was stirred at room temperature for 2 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (methanol:ethyl acetate:hexane=0:50:50 to 10:90:0, volume ratio) to give an orange oil. The obtained orange oil was purified by preparative HPLC to give the title compound (150 mg, yield 49%) as a white amorphous solid.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. customto give an orange oil
  8. customThe obtained orange oil was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-c6f2b21354334e5bb2573cca83509aab
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557805B2

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