Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylate

HRID 662087

Reaktionsgleichung

Reaktionsgleichung von HRID 662087
[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[CH:7][CH:6]=1)=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:39][CH2:40][C:41]1[C:46]([CH2:47][CH3:48])=[N:45][C:44]2[N:49]([CH2:52][CH3:53])[N:50]=[CH:51][C:43]=2[C:42]=1[NH:54][CH:55]1[CH2:60][CH2:59][O:58][CH2:57][CH2:56]1>ClCCl>[CH2:52]([N:49]1[C:44]2=[N:45][C:46]([CH2:47][CH3:48])=[C:41]([CH2:40][NH:39][C:11]([C:9]3[N:10]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=[CH:7][CH:8]=3)=[O:13])[C:42]([NH:54][CH:55]3[CH2:56][CH2:57][O:58][CH2:59][CH2:60]3)=[C:43]2[CH:51]=[N:50]1)[CH3:53]

Komponenten

5

Edukt 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 40191726-(Methoxycarbonyl)pyridine-2-carboxylic acidHCID 670055525-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride

Produkt 1

HCID 57819362methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylateAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

6-[(Methyloxy)carbonyl]-2-pyridinecarboxylic acid (272 mg, 1.500 mmol) was dissolved in dichloromethane (50 mL) and stirred under argon at room temperature. Then HBTU (569 mg, 1.500 mmol) was added followed by 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride (510 mg, 1.5 mmol) and then the TEA (0.418 mL, 3.00 mmol). The mixture was stirred under argon overnight. The solvent was evaporated, and the residue partitioned between EtOAc (75 mL) and water (25 ml). The organic phase was washed with water (3×25 mL), brine, dried over anhydrous sodium sulfate, filtered and evaporated to give the crude residue. It was purified by CombiFlash on a 12 gram silica column eluted with 60-100% EtOAc in hexane. Product fractions were combined and concentrated to give methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylate (609 mg, 1.305 mmol, 87% yield) as a white solid. LC-MS m/z 467 (M+H)+, 0.74 min (ret time).

Aufarbeitung

  1. stirringThe mixture was stirred under argon overnight
  2. customThe solvent was evaporated
  3. customthe residue partitioned between EtOAc (75 mL) and water (25 ml)
  4. washThe organic phase was washed with water (3×25 mL), brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude residue
  9. customIt was purified by CombiFlash on a 12 gram silica column
  10. washeluted with 60-100% EtOAc in hexane
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-ab90fde0c8b34a8b9c61c5be17d68885
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084449B2

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