Benzyl Bromide → 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [2-(4-benzyloxypiperidin-1-yl)-1-(S)-(4-fluorobenzyl)-2-oxoethyl]amide

HRID 1693462ノート

反応式

HRID 1693462 の反応式
[F:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C@H:7]([NH:17][C:18]([C:20]2[NH:29][C:23]3=[CH:24][N:25]=[C:26]([Cl:28])[CH:27]=[C:22]3[CH:21]=2)=[O:19])[C:8]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[H-].[Na+]>CN(C=O)C>[CH2:32]([O:16][CH:13]1[CH2:12][CH2:11][N:10]([C:8](=[O:9])[C@@H:7]([NH:17][C:18]([C:20]2[NH:29][C:23]3=[CH:24][N:25]=[C:26]([Cl:28])[CH:27]=[C:22]3[CH:21]=2)=[O:19])[CH2:6][C:5]2[CH:30]=[CH:31][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:15][CH2:14]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

参加物

5

反応物 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 116986775-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide

生成物 1

HCID 597537585-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [2-(4-benzyloxypiperidin-1-yl)-1-(S)-(4-fluorobenzyl)-2-oxoethyl]amide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide (EXAMPLE 5, 50 mg, 0.11 mmol) in anhydrous DMF (3 mL) under argon was added benzylbromide (16 μl, 0.13 mmol) followed by sodium hydride (6.3 mg, 0.16 mmol) and the reaction stirred for 16 h. Solvent was removed in vacuo and the residue partitioned between ethyl acetate (2×20 mL) and water (20 mL). The organic fractions were washed with 1M HCl (20 mL), NaHCO3 (2×20 mL) then brine (2×20 mL), dried (MgSO4) and the solvent removed in vacuo. Crude material was purified by chromatography on silica gel with dichloromethane/methanol (9:1) as the eluent to give the title compound as an off-white powder. m/z (ES+)=535.33 [M+H]+; RT=3.44 min.

後処理

  1. customSolvent was removed in vacuo
  2. customthe residue partitioned between ethyl acetate (2×20 mL) and water (20 mL)
  3. washThe organic fractions were washed with 1M HCl (20 mL), NaHCO3 (2×20 mL)
  4. dry with materialbrine (2×20 mL), dried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customCrude material was purified by chromatography on silica gel with dichloromethane/methanol (9:1) as the eluent

出典と根拠

ORDレコード
ord-31e8ca724c7f4886b84060221d44cc67
出典データセット
uspto-grants-2012_04
特許番号
US08158622B2

反応ノート

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