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

HRID 397656

반응식

HRID 397656 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-04078c9d88f44345a821acd7ecd88e5c
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06610707B1

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