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Ethanol → 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80807
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 80807
C(O)C.[Cl:4][C:5]1[C:6]([CH:49]([CH3:51])[CH3:50])=[N:7][N:8]([CH3:48])[C:9]=1[N:10]1[CH2:47][CH2:46][C:13]2[N:14]=[C:15]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:45])=[CH:29][N:30]4S(C3C=CC(C)=CC=3)(=O)=O)[N:16]=[C:17]([N:18]3[CH2:23][CH2:22][CH2:21][C:20]([CH3:25])([CH3:24])[CH2:19]3)[C:12]=2[CH2:11]1.[OH-].[K+].[OH-].[NH4+]>ClCCl.O>[Cl:4][C:5]1[C:6]([CH:49]([CH3:51])[CH3:50])=[N:7][N:8]([CH3:48])[C:9]=1[N:10]1[CH2:47][CH2:46][C:13]2[N:14]=[C:15]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:45])=[CH:29][NH:30]4)[N:16]=[C:17]([N:18]3[CH2:23][CH2:22][CH2:21][C:20]([CH3:25])([CH3:24])[CH2:19]3)[C:12]=2[CH2:11]1
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Komponenten

7

Edukt 4

HCID 702EthanolHCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 712405676-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Produkt 1

HCID 71244742
6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Ethanol (1.8 mL) was added to 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (74 mg, 0.108 mmol) in a microwave vial. Next, KOH (61 mg, 1.08 mmol) was added followed by 28% aqueous ammonium hydroxide (0.6 mL, 4.35 mmol). The vessel was sealed and heated via microwave irradiation at 100° C. for 75 minutes. The reaction mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the organic layer was dried by passing through a phase separator. The eluent was concentrated and the resulting residue was purified by reverse phase HPLC (20-55% MeCN/Water (0.1% TFA)). The eluent from the HPLC was neutralized with saturated aqueous sodium bicarbonate and extracted with dichloromethane. The organic extract was dried by passing through a phase separator and concentrating to provide 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine.

Aufarbeitung

  1. customThe vessel was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe layers were separated
  4. customthe organic layer was dried
  5. concentrationThe eluent was concentrated
  6. customthe resulting residue was purified by reverse phase HPLC (20-55% MeCN/Water (0.1% TFA))
  7. extractionextracted with dichloromethane
  8. extractionThe organic extract
  9. customwas dried
  10. concentrationconcentrating

Quellen und Nachweise

ORD-Eintrag
ord-dfa0d04715a6440982c5f98e234893cf
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08846656B2

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