1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid tert-butyl ester

HRID 1693485Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1693485
[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.[C:15]([O:19][C:20](=[O:31])[C@@H:21]([NH2:30])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)([CH3:18])([CH3:17])[CH3:16].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[C:15]([O:19][C:20](=[O:31])[C@@H:21]([NH:30][C:11]([C:9]1[NH:8][C:5]2=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]2[CH:10]=1)=[O:13])[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)([CH3:18])([CH3:16])[CH3:17]

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 67278629tert-butyl (2S)-2-amino-3-(4-fluorophenyl)propanoate hydrochloride

Produkt 1

HCID 597535552-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (Preparation 57, 500 mg, 2.54 mmol) in DMF (20 mL) was added 2-(S)-amino-3-(4-fluorophenyl)propionic acid tert-butyl ester hydrochloride (Preparation 114, 701 mg, 2.54 mmol), HOBt (344 mg, 2.54 mmol) and DIPEA (1.4 mL, 7.88 mmol). After 5 min, EDCI (634 mg, 3.31 mmol) was added and the reaction mixture stirred at rt for 72 h. The solvent was removed in vacuo and the solid partitioned between water (50 mL) and ethyl acetate (3×40 mL). The combined organic phase was washed with brine (20 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography on silica gel eluting with methanol:dichloromethane (1:99) to give the title compound. δH (CD3OD): 1.42 (9H, s), 3.09 (1H, dd), 3.22 (1H, dd), 4.76 (1H, m), 6.98 (2H, m), 7.07 (1H, s), 7.27 (2H, m), 8.06 (1H, d), 8.28 (1H, d); m/z (ES+)=418 [M+H]+.

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. customthe solid partitioned between water (50 mL) and ethyl acetate (3×40 mL)
  3. washThe combined organic phase was washed with brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by chromatography on silica gel eluting with methanol:dichloromethane (1:99)

Quellen und Nachweise

ORD-Eintrag
ord-145e1bbb1950479cb01c002bc0cb3b71
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158622B2

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