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 1193422노트

반응식

HRID 1193422 반응식
[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]

참가 물질

5

반응물 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

생성물 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 amide수율 59%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-81190dde29c64187a0948fa01f40525a
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680159B2

반응 노트

불러오는 중…