Cesium carbonate → (3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amide

HRID 1193422Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1193422
[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:18]([CH3:25])[CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5].Cl[C:31]1[S:35][N:34]=[C:33]([CH3:36])[N:32]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:18]([CH3:25])[CH:19]3[CH2:20][CH2:21][N:22]([C:31]4[S:35][N:34]=[C:33]([CH3:36])[N:32]=4)[CH2:23][CH2:24]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 129191595-Chloro-3-methyl-1,2,4-thiadiazoleHCID 66798745(R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide

Produkt 1

HCID 56942444(3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of (R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide (see stage 2 illustrative compound H-214) (230 mg, 0.559 mmol, 1 eq), 5-chloro-3-methyl-1,2,4-thiadiazole (83 mg, 0.615 mmol, 1.1 eq) and Cs2CO3 (363 mg, 1.118 mmol, 2 eq) in dioxane (10 ml) was heated for 2 h at 80° C. When the reaction was complete according to TLC monitoring, the reaction mixture was concentrated under reduced pressure. The residue was taken up in dichloromethane (50 ml), washed with water (30 ml) and saturated sodium chloride solution (30 ml) and dried over sodium sulfate. The solvent was removed by distillation under reduced pressure and the crude product was purified by column chromatography (Alox, 0.5% methanol/dichloromethane). The desired product was in the form of a white solid. Yield: 59% (170 mg, 0.333 mmol)

Aufarbeitung

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. washwashed with water (30 ml) and saturated sodium chloride solution (30 ml)
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed by distillation under reduced pressure
  5. customthe crude product was purified by column chromatography (Alox, 0.5% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-81190dde29c64187a0948fa01f40525a
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680159B2

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