Dichloromethane → (R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid

HRID 1625468Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1625468
C[O:2][C:3](=[O:48])[CH2:4][C@H:5]([C:25]1[S:26][C:27]([C:30]2[C:38]3[C:33](=[N:34][CH:35]=[CH:36][CH:37]=3)[N:32](S(C3C=CC=CC=3)(=O)=O)[CH:31]=2)=[CH:28][CH:29]=1)[NH:6][C:7]([C:9]1[C:10](=[O:24])[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=2)[CH:12]=[CH:13][CH:14]=1)=[O:8].C(Cl)Cl>C[O-].[Na+].CO>[F:23][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[F:22])[CH2:15][N:11]1[CH:12]=[CH:13][CH:14]=[C:9]([C:7]([NH:6][C@@H:5]([C:25]2[S:26][C:27]([C:30]3[C:38]4[C:33](=[N:34][CH:35]=[CH:36][CH:37]=4)[NH:32][CH:31]=3)=[CH:28][CH:29]=2)[CH2:4][C:3]([OH:48])=[O:2])=[O:8])[C:10]1=[O:24]

Komponenten

5

Edukt 2

HCID 6344DichloromethaneHCID 68609564(R)-3-[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

Produkt 1

HCID 59362416(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 10942334Sodium MethoxideLösungsmittel

Versuchsvorschrift

(R)-3-[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester (0.050 g, 0.000072 mol;) was dissolved in 0.5 M of Sodium methoxide in methanol (3 mL) and Methylene chloride (3 g, 0.04 mol;). The reaction was heated at 75 C for 1 hour. LC-MS showed the disappearance of starting material and the appearance of product at 1.25 535.55. Some methyl ester and acid were seen but by the time it was injected on gilson only acid was present. The reaction was concentrated and dissolved in DMSO and methanol 1:1 for purification by Gilson Preparative HPLC. Pure fractions were combined and concentrated. ES (+) MS m/e=535.55; NMR (400 MHz, DMSO-d6) δ ppm 2.98 (d, 2H, J=7 Hz), 5.22 (s, 2H,), 5.66 (m, 1H), 6.66 (t, 1H, J=8 Hz), 7.03 (d, 1H, J=3 Hz), 7.14-7.20 (m, 2H), 7.22 (d, 1H, J=4 Hz), 7.38-7.49 (m, 2H), 7.81 (m, 1H), 8.2-8.25 (m, 2H), 8.29 (m, 1H), 8.4 (dd. 1H), 10.27 (d, 1H)

Aufarbeitung

  1. temperatureThe reaction was heated at 75 C for 1 hour
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in DMSO
  4. custommethanol 1:1 for purification by Gilson Preparative HPLC
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-eb70e980ed36494495d639ba281a4813
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778977B2

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