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Lithium hydroxide, monohydrate → 4-{5-[(1,4-diazabicyclo[2.2.2]oct-2-ylmethyl)amino]pyrazin-2-yl}-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylic acid

HRID 655745
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 655745
[N:1]12[CH2:8][CH2:7][N:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[CH2:9][NH:10][C:11]1[N:12]=[CH:13][C:14]([C:17]2[N:18]=[C:19]([N:27]3[CH2:32][CH2:31][C@@H:30]([NH:33][C:34]([C:36]4[NH:37][C:38]([CH3:43])=[C:39]([Cl:42])[C:40]=4[Cl:41])=[O:35])[C@@H:29]([O:44][CH3:45])[CH2:28]3)[S:20][C:21]=2[C:22]([O:24]CC)=[O:23])=[N:15][CH:16]=1.O.[OH-].[Li+]>CO.O>[N:1]12[CH2:8][CH2:7][N:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[CH2:9][NH:10][C:11]1[N:12]=[CH:13][C:14]([C:17]2[N:18]=[C:19]([N:27]3[CH2:32][CH2:31][C@@H:30]([NH:33][C:34]([C:36]4[NH:37][C:38]([CH3:43])=[C:39]([Cl:42])[C:40]=4[Cl:41])=[O:35])[C@@H:29]([O:44][CH3:45])[CH2:28]3)[S:20][C:21]=2[C:22]([OH:24])=[O:23])=[N:15][CH:16]=1
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Komponenten

5

Edukt 2

HCID 168937Lithium hydroxide, monohydrateHCID 59402477ethyl 4-{5-[(1,4-diazabicyclo[2.2.2]oct-2-ylmethyl)amino]pyrazin-2-yl}-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate

Produkt 1

HCID 594024554-{5-[(1,4-diazabicyclo[2.2.2]oct-2-ylmethyl)amino]pyrazin-2-yl}-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylic acidAusbeute 70,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

Ethyl 4-{5-[(1,4-diazabicyclo[2.2.2]oct-2-ylmethyl)amino]pyrazin-2-yl}-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate (Example 194, 100 mg, 0.14 mmol) was dissolved in methanol (3 mL) and water (1 mL). Lithium hydroxide monohydrate (18 mg, 0.44 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. The methanol was completely evaporated. The resulting crude product was taken in water (20 mL) and acidified to pH 6 with 2N hydrochloric acid (1.0 mL). The aqueous layer was concentrated to a residue, which was purified by preparative thin layer chromatography to afford 64 mg (66.8%) of 4-{5-[(1,4-diazabicyclo[2.2.2]oct-2-ylmethyl)amino]pyrazin-2-yl}-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylic acid as a light yellow solid.

Aufarbeitung

  1. customThe methanol was completely evaporated
  2. concentrationThe aqueous layer was concentrated to a residue, which
  3. customwas purified by preparative thin layer chromatography

Quellen und Nachweise

ORD-Eintrag
ord-c3a1620d6bb8406fb6eeea424c9a9cec
Quelldatensatz
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08071605B2

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