1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid [1-(S)-(4-fluoro-benzyl)-2-(3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide

HRID 1693487ノート

反応式

HRID 1693487 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[N:6][CH:7]=1.Cl.[NH2:15][C@@H:16]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:17]([N:19]1[CH2:23][CH2:22][C@H:21]([OH:24])[CH2:20]1)=[O:18].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[F:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][C@H:16]([NH:15][C:11]([C:9]2[NH:8][C:5]3=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[CH:10]=2)=[O:13])[C:17]([N:19]2[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20]2)=[O:18])=[CH:27][CH:28]=1

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 446307055-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acidHCID 672789012-(S)-amino-3-(4-fluorophenyl)-1-(3-(S)-hydroxypyrrolidin-1-yl)propan-1-one hydrochloride

生成物 1

HCID 672794245-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid [1-(S)-(4-fluoro-benzyl)-2-(3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (Preparation 57, 34 mg, 0.17 mmol) in DMF (5 mL) was added 2-(S)-amino-3-(4-fluorophenyl)-1-(3-(S)-hydroxypyrrolidin-1-yl)propan-1-one hydrochloride (Preparation 103, 50 mg, 0.17 mmol), HOBt (23 mg, 0.17 mmol) and DIPEA (94 μL, 0.54 mmol). After 5 min, EDCI (43 mg, 0.23 mmol) was added and the reaction stirred at rt for 16 h. The solvent was removed in vacuo and the residue partitioned between water (25 mL) and ethyl acetate (3×20 mL). The combined organic layer was washed with 2N sodium hydroxide solution (2×10 mL), brine (10 mL), dried (MgSO4) and concentrated in vacuo. Purification via chromatography on silica gel eluting with methanol:dichloromethane (7:93) gave the title compound. m/z (ES+)=431 [M+H]+; RT=3.49 min.

後処理

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between water (25 mL) and ethyl acetate (3×20 mL)
  3. washThe combined organic layer was washed with 2N sodium hydroxide solution (2×10 mL), brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification via chromatography on silica gel eluting with methanol:dichloromethane (7:93)

出典と根拠

ORDレコード
ord-1cc615adfb7043d6bd368eff8c429d3c
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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