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 1645252ノート

反応式

HRID 1645252 の反応式
[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

参加物

7

反応物 6

HCID 313Hydrochloric AcidHCID 6344Dichloromethane3 回HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2 回HCID 57819715(S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid

生成物 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 hydrochloride収率 43%

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-9aa444f1287448b39b4d29b3b28c6620
出典データセット
uspto-grants-2012_02
特許番号
US08124624B2

反応ノート

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