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

HRID 397656

Reaction equation

HRID 397656 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-04078c9d88f44345a821acd7ecd88e5c
Source dataset
uspto-grants-2003_08
Patent number
US06610707B1

Linked notes

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