Methanesulfonic Acid → 1-(4-(5-bromopent-1-yn-1-yl)phenyl)-3-((1,6-diethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)urea

HRID 385268Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 385268
[Br:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=1.CS(O)(=O)=O.C(N(CC)CC)C.Cl[C:27](Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.Cl.[NH2:40][CH2:41][C:42]1[C:47]([CH2:48][CH3:49])=[N:46][C:45]2[N:50]([CH2:53][CH3:54])[N:51]=[CH:52][C:44]=2[C:43]=1[NH:55][CH:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1>ClCCl>[Br:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:8]=[CH:9][C:10]([NH:11][C:27]([NH:40][CH2:41][C:42]2[C:43]([NH:55][CH:56]3[CH2:57][CH2:58][O:59][CH2:60][CH2:61]3)=[C:44]3[CH:52]=[N:51][N:50]([CH2:53][CH3:54])[C:45]3=[N:46][C:47]=2[CH2:48][CH3:49])=[O:29])=[CH:12][CH:13]=1

Komponenten

7

Edukt 5

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 94429TriphosgeneHCID 575175844-(5-Bromopent-1-yn-1-yl)anilineHCID 669893455-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine dihydrochloride

Produkt 1

HCID 585052951-(4-(5-bromopent-1-yn-1-yl)phenyl)-3-((1,6-diethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)urea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A suspension of Intermediate 24 methanesulfonic acid salt (1.4 g, 4.2 mmol) in dichloromethane (50 mL) was treated with triethylamine (8.8 mL, 63 mmol) and then the mixture was cooled in an ice-water bath and treated with triphosgene (0.93 g, 3.2 mmol), followed by 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine dihydrochloride (1.3 g, 3.4 mmol). The mixture was quenched by the addition of methanol and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate. The combined organics were washed with a 5% aqueous potassium hydrogen sulfate solution and saturated aqueous sodium chloride solution and then concentrated under reduced pressure. The crude residue was purified via automated flash silica gel chromatography, using a SiliSep flash column (dichloromethane/methanol/ammonium hydroxide). Concentration of the desired fractions under reduced pressure provided the title compound as a pale tan foam. ES/MS calcd. for C28H36BrN6O2+ 567.2. found m/z=567.2 (M+H)+.

Aufarbeitung

  1. temperaturethe mixture was cooled in an ice-water bath
  2. customThe mixture was quenched by the addition of methanol
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and water
  5. extractionThe aqueous phase was extracted twice with ethyl acetate
  6. washThe combined organics were washed with a 5% aqueous potassium hydrogen sulfate solution and saturated aqueous sodium chloride solution
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified via automated flash silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-ba9ce21e9eef455fb38ceed7f4d034ef
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367829B2

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