Sodium Carbonate → HCID 178481012, Verbindung

HRID 432178

Reaktionsgleichung

Reaktionsgleichung von HRID 432178
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[O:25]([C:32]1[N:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C@H:15]2[CH2:16][CH2:17][C@H:12]([N:4]3[C:5]4=[N:6][CH:7]=[N:8][C:9]([NH2:11])=[C:10]4[C:2]([C:35]4[CH:34]=[N:33][C:32]([O:25][C:26]5[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=5)=[N:37][CH:36]=4)=[N:3]3)[CH2:13][CH2:14]2)[CH2:19][CH2:20]1

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 223468822-Phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyrimidineHCID 178481015HCID 178481015, Verbindung

Produkt 1

HCID 178481012HCID 178481012, VerbindungAusbeute 47,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A mixture of trans 3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AD) (0.300 g, 0.00068 mol), 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (int AV) (0.304 g, 0.00102 mol), sodium carbonate (0.180 g, 0.00170 mol) in 1,2-dimethoxyethane (10 mL) and water (20 mL) was stirred rapidly and tetrakis(triphenylphosphine)palladium(0) (0.047 g, 0.000040 mol) added. The reaction mixture was stirred 18 hours at 80° C. The solvents were removed in vacuo and the residue was partitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate (3×25 mL). The combined organic phases were dried over magnesium sulfate, and the solvent was removed in vacuo. The product was purified by flash column chromatography on silica using dichloromethane/methanol/ammonium hydroxide (95:5:0.5). The solvent was removed in vacuo to give trans-1-[4-(4-methylpiperazino)cyclohexyl]-3-(2-phenoxy-5-pyrimidinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.155 g, 0.00032 mol): 1H NMR (DMSO-d6, 400 MHz) 8.78 (s, 2H), 8.25 (s, 1H), 7.48 (t, 2H), 7.28 (t, 1H), 7.27 (d, 2H), 4.65 (m, 1H), 1.44-2.36 (m, 20H); TLC (dichloromethane/methanol/ammonium hydroxide=90:10:0.5) Rf 0.33.

Aufarbeitung

  1. stirringThe reaction mixture was stirred 18 hours at 80° C
  2. customThe solvents were removed in vacuo
  3. customthe residue was partitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate (50 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×25 mL)
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. customthe solvent was removed in vacuo
  8. customThe product was purified by flash column chromatography on silica
  9. customThe solvent was removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d545f723e5fd4b6992ee78a5ec1ad1a7
Quelldatensatz
uspto-grants-2003_12
Patentnummer
US06660744B1

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