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 1193422ノート

反応式

HRID 1193422 の反応式
[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]

参加物

5

反応物 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

生成物 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 amide収率 59%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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)

後処理

  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)

出典と根拠

ORDレコード
ord-81190dde29c64187a0948fa01f40525a
出典データセット
uspto-grants-2014_03
特許番号
US08680159B2

反応ノート

読み込み中…