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

HRID 1193425노트

반응식

HRID 1193425 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[CH:36]=[CH:35][N:34]=[C:33](CN)[N:32]=1.C[CH2:40][N:41](C(C)C)C(C)C>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:35]4[CH:36]=[CH:31][N:32]=[C:33]([NH:41][CH3:40])[N:34]=4)[CH2:23][CH2:24]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 22460689(4-Chloropyrimidin-2-YL)methanamineHCID 66798745(R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide

생성물 1

HCID 66798485(3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(2-methylamino-pyrimidin-4-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amide수율 49%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

A mixture of (R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide (400 mg, 0.973 mmol, 1 eq), (4-chloropyrimidin-2-yl)methylamine (280 mg, 1.946 mmol, 2 eq) and DIPEA (0.33 ml, 1.946 mmol, 2 eq) in dioxane (10 ml) was refluxed for 16 h. When the reaction was complete according to TLC monitoring, concentration under reduced pressure was carried out and the residue was taken up in dichloromethane (100 ml) and washed with water (40 ml) and saturated sodium chloride solution (40 ml). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 6% methanol in dichloromethane). The desired product was in the form of a white solid. Yield: 49% (250 mg, 0.482 mmol)

후처리

  1. temperaturewas refluxed for 16 h
  2. concentrationWhen the reaction was complete according to TLC monitoring, concentration under reduced pressure
  3. washwashed with water (40 ml) and saturated sodium chloride solution (40 ml)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica gel, 6% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-6bcc00b5450949dc97599b25f3778581
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680159B2

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