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 1693487Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1693487
[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

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-1cc615adfb7043d6bd368eff8c429d3c
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158622B2

Notizen zur Reaktion

Wird geladen…