Sodium Carbonate → (2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

HRID 500718Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 500718
I[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=2)=[CH:5][N:4]([CH:18]([CH3:20])[CH3:19])[N:3]=1.[CH3:21][NH:22][C:23]1[C:28]([CH3:29])=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=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:18]([N:4]1[CH:5]=[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=2)[C:2]([C:26]2[CH:25]=[N:24][C:23]([NH:22][CH3:21])=[C:28]([CH3:29])[CH:27]=2)=[N:3]1)([CH3:20])[CH3:19]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 57416512N,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-amineHCID 57856239(2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

Produkt 1

HCID 25181760(2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-olAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of (2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-1-3) (1 g, 2.58 mmol) in toluene (30 mL) and EtOH (10 mL) were added N,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (B-4-3) (2 g, 6.3 mmol in theory) and 2 N aq. Na2CO3 (4 mL). The resulting mixture was degassed under N2 for 2 minutes. Then Pd(PPh3)4 (0.3 g, 0.26 mmol) was added and the mixture was degassed again. The reaction was heated to 80-90° C. and stirred overnight. MS showed the reaction was complete and the mixture was cooled. The organic layer was separated and concentrated. The residue was purified by prep. HPLC to afford (2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-4) (0.167 g, 16.98%) as a light yellow solid.

Aufarbeitung

  1. customThe resulting mixture was degassed under N2 for 2 minutes
  2. customthe mixture was degassed again
  3. temperaturethe mixture was cooled
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customThe residue was purified by prep

Quellen und Nachweise

ORD-Eintrag
ord-fe1c12ddddec40f6a097625b6a29b2db
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772246B2

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