Hydrochloric Acid → 2-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-y]-methoxy]-1-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethanone hydrochloride

HRID 1645252노트

반응식

HRID 1645252 반응식
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]2[CH2:19][O:20][CH2:21][C:22](O)=[O:23])(=[O:12])=[O:11])=[C:5]([CH3:25])[CH:4]=1.[CH3:26][CH2:27][N:28]([CH:32]([CH3:34])C)[CH:29]([CH3:31])C.CCN=C=N[CH2:40][CH2:41][CH2:42][N:43]([CH3:45])C.Cl.[CH:47]1[CH:48]=[CH:49][C:50]2N(O)N=[N:53][C:51]=2C=1.[Cl:57][CH2:58]Cl>>[ClH:57].[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:25])[C:6]([S:10]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]2[CH2:19][O:20][CH2:21][C:22]([N:53]2[CH2:47][CH2:48][C:49]([C:58]3[CH:45]=[N:43][CH:42]=[CH:41][CH:40]=3)([CH2:34][CH2:32][N:28]3[CH2:27][CH2:26][CH2:31][CH2:29]3)[CH2:50][CH2:51]2)=[O:23])(=[O:12])=[O:11])=[C:7]([CH3:9])[CH:8]=1

참가 물질

7

반응물 6

HCID 313Hydrochloric AcidHCID 6344Dichloromethane3회HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2회HCID 57819715(S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid

생성물 1

HCID 442524462-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-y]-methoxy]-1-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethanone hydrochloride수율 43%

실험 절차

To a solution of 2-(2-(4-methoxy-2,6-dimethylphenylsulfonyl)benzyloxy)acetic acid [carboxylic acid 1] (0.5 mmol) in dichloromethane (5 ml) were added DIPEA (4 eq.), EDCI. HCl (1.2 eq) and HOBt (1 eq.). Then a mixture of Boc-deprotected tert-butyl 4-(pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethyl)piperidine-1-carboxylate (0.62 mmol) [deprotected using standard reaction conditions: dichloromethane (3 ml), TFA (3 eq.) and concentration in vacuo] and DIPEA (2 eq.) in dichloromethane (3 ml) was added dropwise at ice-cold reaction conditions. The reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane, washed with saturated ammonium chloride, brine, saturated sodium bicarbonate solution and again brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica, methanol/dichloromethane). The free base of the desired compound was dissolved in dioxane (3 ml), stirred in dioxane saturated with HCl for 1 h and then concentrated under reduced pressure to give the desired product.

후처리

  1. additionwas added dropwise at ice-cold reaction conditions
  2. washwashed with saturated ammonium chloride, brine, saturated sodium bicarbonate solution and again brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (silica, methanol/dichloromethane)
  6. dissolutionThe free base of the desired compound was dissolved in dioxane (3 ml)
  7. stirringstirred in dioxane saturated with HCl for 1 h
  8. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-9aa444f1287448b39b4d29b3b28c6620
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08124624B2

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