Sodium Carbonate → tert-butyl 4-{[4-amino-3-(4-{[(benzyloxy)carbonyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl}-4-hydroxy-1-piperidinecarboxylate

HRID 897812Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 897812
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3([OH:26])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[N:9]=[C:10](I)[C:3]=12.[CH3:27][O:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[CH:31][C:30]=1[NH:44][C:45](=[O:54])[O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=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>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3([OH:26])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[N:9]=[C:10]([C:33]3[CH:32]=[CH:31][C:30]([NH:44][C:45]([O:46][CH2:47][C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[O:54])=[C:29]([O:28][CH3:27])[CH:34]=3)[C:3]=12

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 22346787benzyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 22347243tert-butyl 4-[(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl]-4-hydroxy-1-piperidinecarboxylate

Produkt 1

HCID 22346931tert-butyl 4-{[4-amino-3-(4-{[(benzyloxy)carbonyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl}-4-hydroxy-1-piperidinecarboxylateAusbeute 29,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of tert-butyl 4-[(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl]-4-hydroxy-1-piperidinecarboxylate (0.27 g, 0.00057 mol), benzyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (0.26 g, 0.00068 mol), tetrakis(triphenylphosphine)palladium (0.039 g, 0.000034 mol) and sodium carbonate (0.15 g, 0.0014 mol) in ethylene glycol dimethyl ether (7 mL) and water (3 mL) was heated at 85° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and ethylene glycol dimethyl ether was removed under the reduced pressure. The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic extracts were washed with water and brine, and dried over magnesium sulfate. The organic layer was filtered through silica gel twice to remove the catalyst, and the solvent was removed under reduced pressure. The residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min) to yield tert-butyl 4-{[4-amino-3-(4-{[(benzyloxy)carbonyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl}-4-hydroxy-1-piperidinecarboxylate (0.1 g, 0.00017 mol).

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. customethylene glycol dimethyl ether was removed under the reduced pressure
  3. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe organic layer was filtered through silica gel twice
  7. customto remove the catalyst
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-c30523a5db2c43e89197bc63b70f84f5
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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