Ammonia → 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}acetamide

HRID 1042152노트

반응식

HRID 1042152 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.C[N:38](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.N>CCCCCC.C(OCC)(=O)C.CO.O.CN(C)C=O>[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[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[CH:19]=2)[NH:16][C:15]([C:27]2[S:28][CH:29]([CH2:32][C:33]([NH2:38])=[O:35])[CH2:30][N:31]=2)=[CH:14]3)=[CH:6][CH:5]=1

참가 물질

10

반응물 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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 667261272-{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}acetamide수율 45.1%

시약·촉매·용매 5

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

반응 조건

온도
50 °C

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 (400 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (308 mg), 1-hydroxybenzotriazole (135 mg), and N,N-dimethylformamide (15 mL) was stirred at 50° C. for 30 min. The reaction solution was cooled to room temperature, 10% aqueous ammonia solution (1.5 mL) was added, and the mixture was stirred at room temperature for 2.5 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 15:85:0, volume ratio) to give an orange oil. The obtained orange oil was purified by preparative HPLC to give the title compound (180 mg, yield 45%) as a white amorphous solid.

후처리

  1. temperatureThe reaction solution was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature for 2.5 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained crude product
  9. customto give an orange oil
  10. customThe obtained orange oil was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-0536b808924d469ba2dfdc5b9b35d31e
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557805B2

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