Hydrochloric Acid → 3-[4-methoxy-3-[2-oxo-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]acetyl]-1H-pyrrolo[2,3-c]pyridin-7-yl]-1H-pyrazole-5-carboxylic acid

HRID 1157759Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157759
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([O:16]CC)=[O:15])[NH:11][N:10]=2)=[C:5]2[NH:19][CH:20]=[C:21]([C:22](=[O:42])[C:23](=[O:41])[N:24]3[CH2:29][CH2:28][N:27]([C:30]4[N:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[N:33]=[N:32][N:31]=4)[CH2:26][CH2:25]3)[C:4]=12.O[Li].O.Cl>CN(C=O)C.O>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([OH:16])=[O:15])[NH:11][N:10]=2)=[C:5]2[NH:19][CH:20]=[C:21]([C:22](=[O:42])[C:23](=[O:41])[N:24]3[CH2:25][CH2:26][N:27]([C:30]4[N:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[N:33]=[N:32][N:31]=4)[CH2:28][CH2:29]3)[C:4]=12

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 24875208ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate

Produkt 1

HCID 248747543-[4-methoxy-3-[2-oxo-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]acetyl]-1H-pyrrolo[2,3-c]pyridin-7-yl]-1H-pyrazole-5-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel3×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a suspension of ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate (0.124 g, 0.217 mmol) in DMF (1.5 mL) and H2O (1.5 mL) was added LiOH monohydrate (0.027 g, 0.651 mmol). The mixture was heated to 120° C. for 24 h. The reaction was not complete, so an additional 0.05 g of LiOH hydrate along with 2 mL of H2O were added to the mixture, and it was again heated to 120° C. After 24 h of heating, the reaction was nearly complete by LCMS, so it was cooled to rt, and made acidic (pH=1) with 6N HCl. The mixture was diluted with H2O, and partitioned with EtOAc. The product precipitated from between the two layers, and was collected by filtration. The solids were washed with cold MeOH and H2O. The 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylic acid (0.08 g) was collected as a light yellow solid. LCMS: m/e 542.97 (M+H)+, ret time 1.86 min (method 2). 1H NMR (500 MHz, DMSO-D6) δ ppm 12.10-12.22 (s, 1H) 8.25 (s, 1H) 8.10 (s, 1H) 7.56-7.77 (m, 5H) 7.39 (s, 1H) 3.99 (s, 3H) 3.67-3.72 (m, 2H) 3.40-3.46 (m, 2H) 3.29-3.36 (m, 2H) 3.14-3.20 (m, 2H).

Aufarbeitung

  1. temperaturewas again heated to 120° C
  2. temperatureAfter 24 h of heating
  3. temperaturewas cooled to rt
  4. custompartitioned with EtOAc
  5. customThe product precipitated from between the two layers
  6. filtrationwas collected by filtration
  7. washThe solids were washed with cold MeOH and H2O
  8. customThe 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylic acid (0.08 g) was collected as a light yellow solid
  9. customm/e 542.97 (M+H)+, ret time 1.86 min (method 2)

Quellen und Nachweise

ORD-Eintrag
ord-53209d94e8de4ccdb124ac6e58f7d54e
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807676B2

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