Triethylamine → 2-[4-(3-[(2S)-1-cyclohexylmethylsulfonyl-2-piperidyl]-1,2,4-oxadiazol-5-ylmethoxy)benzyl]-1,3-isoindolinedione

HRID 397656

反応式

HRID 397656 の反応式
[CH:1]1([CH2:7][S:8](Cl)(=[O:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C:19]1[N:23]=[C:22]([CH2:24][O:25][C:26]2[CH:43]=[CH:42][C:29]([CH2:30][N:31]3[C:39](=[O:40])[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:32]3=[O:41])=[CH:28][CH:27]=2)[O:21][N:20]=1.C(N(CC)CC)C>ClCCl>[CH:1]1([CH2:7][S:8]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]2[C:19]2[N:23]=[C:22]([CH2:24][O:25][C:26]3[CH:43]=[CH:42][C:29]([CH2:30][N:31]4[C:32](=[O:41])[C:33]5[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=5)[C:39]4=[O:40])=[CH:28][CH:27]=3)[O:21][N:20]=2)(=[O:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 3871475Cyclohexylmethane sulfonyl chlorideHCID 699488362-[4-(3-[(2S)-2-piperidyl]-1,2,4-oxadiazol-5-ylmethoxy)benzyl]-1,3-isoindolinedione hydrochloride

生成物 1

HCID 570981642-[4-(3-[(2S)-1-cyclohexylmethylsulfonyl-2-piperidyl]-1,2,4-oxadiazol-5-ylmethoxy)benzyl]-1,3-isoindolinedione収率 24.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Cyclohexylmethanesulfonyl chloride (359 mg) [King. J. F. et al., J. Am. Chem. Soc., 1992, 114(5), 1743-9] was added to a solution of 2-[4-(3-[(2S)-2-piperidyl]-1,2,4-oxadiazol-5-ylmethoxy)benzyl]-1,3-isoindolinedione hydrochloride (627 mg) [see Preparation 153 and triethylamine (0.4 ml) in dichloromethane (2 ml). The reaction mixture was stirred at room temperature for 18 hours after which time it was heated to 30° C. and stirred for a further 56 hours. The mixture was diluted with dichloromethane and washed with dilute aqueous hydrochloric acid solution, the organic layer dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0 changing to 75:25, by volume, hexane:ethyl acetate to afford 2-[4-(3-[(2S)-1-cyclohexylmethylsulfonyl-2-piperidyl]-1,2,4-oxadiazol-5-ylmethoxy)benzyl]-1,3-isoindolinedione (192 mg).

後処理

  1. temperaturewas heated to 30° C.
  2. stirringstirred for a further 56 hours
  3. washwashed with dilute aqueous hydrochloric acid solution
  4. dry with materialthe organic layer dried over magnesium sulphate
  5. customthe solvent removed under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0 changing to 75:25, by volume, hexane

出典と根拠

ORDレコード
ord-04078c9d88f44345a821acd7ecd88e5c
出典データセット
uspto-grants-2003_08
特許番号
US06610707B1

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