1,2-Dimethoxyethane → 1-{4-amino-2-(ethoxymethyl)-7-[3-(pyrrolidin-1-ylcarbonyl)phenyl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl}-2-methylpropan-2-ol

HRID 598020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 598020
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[N:25]1([C:30]([C:32]2[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=2)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([C:36]3[CH:35]=[CH:34][CH:33]=[C:32]([C:30]([N:25]4[CH2:26][CH2:27][CH2:28][CH2:29]4)=[O:31])[CH:37]=3)=[CH:5][C:4]=2[N:3]=1

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 113564283-(Pyrrolidine-1-carbonyl)phenylboronic acidHCID 589706811-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

Produkt 1

HCID 589707041-{4-amino-2-(ethoxymethyl)-7-[3-(pyrrolidin-1-ylcarbonyl)phenyl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl}-2-methylpropan-2-olAusbeute 27,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A suspension of 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (1.2 g, 3.0 mmol), (3-pyrrolidinylcarbonylphenyl)boronic acid (0.800 g, 3.65 mmol), potassium carbonate (1.4 g, 10.0 mmol), dichlorobis(triphenylphosphine)palladium(II)(0.021 g, 0.030 mmol), DME (13 mL), and water (7 mL) was stirred under a nitrogen atmosphere in a pressure vessel. The vessel was then sealed and heated at 110° C. for 16.5 hours and allowed to cool to room temperature. The volatiles were removed under reduced pressure. The residue was diluted with methanol, and silica gel was added. The mixture was concentrated under reduced pressure. The residue was purified by automated flash chromatography (FLASH 40+M silica cartridge, eluting with 10% to 25% methanol in ethyl acetate). The resulting material was concentrated twice from acetonitrile and then triturated with acetonitrile (100 mL) to provide a solid. The solid was isolated by filtration, washed with acetonitrile, and dried in a vacuum oven at 65° C. to provide 403 mg of 1-{4-amino-2-(ethoxymethyl)-7-[3-(pyrrolidin-1-ylcarbonyl)phenyl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl}-2-methylpropan-2-ol as a white solid, mp 185-187° C.

Aufarbeitung

  1. customThe vessel was then sealed
  2. temperatureto cool to room temperature
  3. customThe volatiles were removed under reduced pressure
  4. additionThe residue was diluted with methanol, and silica gel
  5. additionwas added
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customThe residue was purified by automated flash chromatography (FLASH 40+M silica cartridge, eluting with 10% to 25% methanol in ethyl acetate)
  8. concentrationThe resulting material was concentrated twice from acetonitrile
  9. customtriturated with acetonitrile (100 mL)
  10. customto provide a solid
  11. customThe solid was isolated by filtration
  12. washwashed with acetonitrile
  13. customdried in a vacuum oven at 65° C.

Quellen und Nachweise

ORD-Eintrag
ord-f738e4eb43494d2ea72073f4c331a841
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897609B2

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