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 897812Notes

Reaction equation

HRID 897812 reaction equation
[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

Participants

7

Reactant 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

Product 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-piperidinecarboxylateYield 29.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c30523a5db2c43e89197bc63b70f84f5
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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