Diisopropylethylamine → HCID 131730207, Verbindung

HRID 387598Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 387598
CCN(C(C)C)C(C)C.Cl.Cl.[C:12]1([C:18]2[C:19]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[C:20]3[C:26]([O:27][CH2:28][C@@H:29]([OH:32])[CH2:30][OH:31])=[N:25][NH:24][C:21]3=[N:22][CH:23]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:39]([O:43][C:44]([NH:46][C@H:47]([CH2:51][C:52]1[CH:57]=[CH:56][C:55]([Cl:58])=[CH:54][CH:53]=1)[C:48](O)=[O:49])=[O:45])([CH3:42])([CH3:41])[CH3:40].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:58][C:55]1[CH:56]=[CH:57][C:52]([CH2:51][C@@H:47]([NH:46][C:44](=[O:45])[O:43][C:39]([CH3:41])([CH3:40])[CH3:42])[C:48]([N:36]2[CH2:35][CH2:34][N:33]([C:19]3[C:18]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[CH:23][N:22]=[C:21]4[NH:24][N:25]=[C:26]([O:27][CH2:28][C@@H:29]([OH:32])[CH2:30][OH:31])[C:20]=34)[CH2:38][CH2:37]2)=[O:49])=[CH:53][CH:54]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 68756592(S)-3-(5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-yloxy)propane-1,2-diol dihydrochloride

Produkt 1

HCID 131730207HCID 131730207, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

DIEA (0.055 mL, 0.32 mmol) was added to a solution of (S)-3-(5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-yloxy)propane-1,2-diol dihydrochloride (0.050 g, 0.079 mmol), (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.024 g, 0.079 mmol) and TBTU (0.031 g, 0.095 mmol) in DCM (1 mL) and stirred at room temperature for 1 hour. The reaction was then concentrated to dryness, and the residue was dissolved in THF/MeOH (2 mL, 1:1), and an aqueous LiOH solution (1 mL, 2 M) was added. The reaction was then stirred for an additional 10 minutes. Ethyl acetate (20 mL) was added, and the organic layer was separated, washed with brine (10 mL), and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (ethyl acetate:MeOH, 20:1) to give tert-butyl(R)-3-(4-chlorophenyl)-1-(4-(3-((S)-2,3-dihydroxypropoxy)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate as a solid. The solid was then dissolved in DCM (1 mL), and TFA (0.4 mL) was added. The mixture was stirred at room temperature for 1 hour and concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and HCl in ether (1 mL, 2 N) was added. The resulting solid was collected by filtration to give (R)-2-amino-3-(4-chlorophenyl)-1-(4-(3-((S)-2,3-dihydroxypropoxy)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)propan-1-one dihydrochloride (0.018 g, 36%). MS APCI (+) m/z 551.2 detected.

Aufarbeitung

  1. concentrationThe reaction was then concentrated to dryness
  2. dissolutionthe residue was dissolved in THF/MeOH (2 mL, 1:1)
  3. additionan aqueous LiOH solution (1 mL, 2 M) was added
  4. stirringThe reaction was then stirred for an additional 10 minutes
  5. additionEthyl acetate (20 mL) was added
  6. customthe organic layer was separated
  7. washwashed with brine (10 mL)
  8. dry with materialdried over sodium sulfate
  9. customAfter removal of the solvent
  10. customthe resulting residue was purified by column chromatography (ethyl acetate:MeOH, 20:1)

Quellen und Nachweise

ORD-Eintrag
ord-19db4d6220e844789a6f7e4963d2e50d
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372842B2

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