1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]amide

HRID 1693450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1693450
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:15](O)=[O:16])=[O:12])[NH:8][C:5]2=[CH:6][N:7]=1.Cl.[OH:27][CH:28]1[CH2:31][NH:30][CH2:29]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[F:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C@H:14]([NH:13][C:11]([C:9]2[NH:8][C:5]3=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[CH:10]=2)=[O:12])[C:15]([N:30]2[CH2:31][CH:28]([OH:27])[CH2:29]2)=[O:16])=[CH:20][CH:21]=1

Komponenten

7

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 597536992-(S)-[(5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid

Produkt 1

HCID 114074055-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-(S)-[(5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (100 mg, 0.28 mmol), 3-hydroxyazetidine hydrochloride (Heterocycles, 2002, 56(1-2), 433-442; 30 mg, 0.28 mmol) and HOBt (37 mg, 0.28 mmol) were dissolved in DMF (5 ml) and DIPEA (0.14 ml, 0.83 mmol). After 5 min, EDCI (69 mg, 0.36 mmol) was added and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo and the residue triturated with water. Purification by chromatography on silica gel eluting with methanol:dichloromethane (1:49 to 3:97) gave the title compound as a yellow solid. δH (CD3OD): 3.08-3.21 (2H, m), 3.58-3.63 (0.5H, m), 3.84-3.91 (0.5H, m), 4.03-4.09 (0.5H, m), 4.25-4.32 (0.5H, m), 4.38-4.94 (4H, m), 7.03-7.12 (2H, m), 7.15-7.19 (1H, m), 7.30-7.38 (2H, m), 7.68 (1H, s), 8.59 (1H, s); RT=3.32 min.

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. customthe residue triturated with water
  3. customPurification by chromatography on silica gel eluting with methanol:dichloromethane (1:49 to 3:97)

Quellen und Nachweise

ORD-Eintrag
ord-f68eda44ee7b4dde8351a9b43455082e
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158622B2

Notizen zur Reaktion

Wird geladen…