Sodium Carbonate → (2S)-1-(4-(1-isopropyl-3-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

HRID 500729Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 500729
[CH3:1][C:2]1[NH:19][C:5]2=[N:6][CH:7]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:9]=[C:4]2[CH:3]=1.I[C:21]1[C:25]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH2:33][C@@H:34]([OH:36])[CH3:35])[N:27]=2)=[CH:24][N:23]([CH:37]([CH3:39])[CH3:38])[N:22]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:37]([N:23]1[CH:24]=[C:25]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH2:33][C@@H:34]([OH:36])[CH3:35])[N:27]=2)[C:21]([C:8]2[CH:9]=[C:4]3[CH:3]=[C:2]([CH3:1])[NH:19][C:5]3=[N:6][CH:7]=2)=[N:22]1)([CH3:39])[CH3:38]

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 533986352-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrrolo[2,3-B]pyridineHCID 57856239(2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

Produkt 1

HCID 25181762(2S)-1-(4-(1-isopropyl-3-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-olAusbeute 18,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 21863594Toluene ethanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a suspension of 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (B-7-7) (1.8 g, 2.3 mmol in the theory) and (2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-1-3) (0.45 g, 1.2 mmol) in toluene/EtOH (3:1, 50 mL) was added aq. Na2CO3 (1.7 mL, 2 M). The mixture was degassed under N2 for 2 minutes, Pd(PPh3)4 (0.05 g, 0.042 mmol) was added into the mixture and degassed again. The mixture was stirred at 80° C. for 30 hours. TLC (CH2Cl2: MeOH=20:1) showed that the reaction was complete. Water (50 mL) and EtOAc (50 mL×3) were added into the mixture. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated to give crude product which was purified via prep. HPLC to afford (2S)-1-(4-(1-isopropyl-3-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-7) (0.169 g, 18.6%) as a white solid.

Aufarbeitung

  1. customThe mixture was degassed under N2 for 2 minutes
  2. customdegassed again
  3. additionWater (50 mL) and EtOAc (50 mL×3) were added into the mixture
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto give crude product which
  8. customwas purified via prep

Quellen und Nachweise

ORD-Eintrag
ord-715c54ba036c463b834c825b4bac5076
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772246B2

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