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Methanamine, hydrochloride (1:1) → 2-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamide

HRID 1188999
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1188999
[CH3:1][O:2][CH2:3][CH:4]([CH2:35][O:36][CH3:37])[O:5][C:6]1[CH:7]=[C:8]([O:24][C:25]2[CH:26]=[N:27][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][CH:30]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]1[S:16][CH:17]([CH2:20][C:21](O)=[O:22])[CH2:18][N:19]=1)=[CH:11]2.Cl.[CH2:39]([N:41]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[Cl-].C[NH3+]>CN(C)C=O.C(N(CC)CC)C>[CH3:37][O:36][CH2:35][CH:4]([CH2:3][O:2][CH3:1])[O:5][C:6]1[CH:7]=[C:8]([O:24][C:25]2[CH:26]=[N:27][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][CH:30]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]1[S:16][CH:17]([CH2:20][C:21]([NH:41][CH3:39])=[O:22])[CH2:18][N:19]=1)=[CH:11]2
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Komponenten

7

Edukt 4

HCID 11637Methanamine, hydrochloride (1:1)HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66896936[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Produkt 1

HCID 66897859
2-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamide
Ausbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

A mixture of [2-(7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (180 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (126 mg), 1-hydroxybenzotriazole (88 mg), methylammonium chloride (44 mg), triethylamine (0.09 mL) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 14 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate/hexane=0/50/50 to 5/95/0, volume ratio) to give a white solid. The solid was recrystallized from acetonitrile-diethyl ether to give the title compound (140 mg, 75%) as colorless crystals. MS 563 (MH+). mp 149-151° C.

Aufarbeitung

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in water
  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
  8. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate/hexane=0/50/50 to 5/95/0, volume ratio)
  9. customto give a white solid
  10. customThe solid was recrystallized from acetonitrile-diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-22243037eb8b42e1832e76bb9c04a561
Quelldatensatz
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08673942B2

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