Sodium Carbonate → HCID 178480960, compound

HRID 897453Notes

Reaction equation

HRID 897453 reaction equation
[C:1]1([C:7]([C:9]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:10]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:25]1[C:33]2[C:28](=[N:29][CH:30]=[N:31][C:32]=2[NH2:34])[N:27]([C@H:35]2[CH2:40][CH2:39][C@@H:38]([N:41]3[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]3)[CH2:37][CH2:36]2)[N:26]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)(=O)/C=C\C(O)=O>COCCOC.O.C(O)C>[NH2:34][C:32]1[N:31]=[CH:30][N:29]=[C:28]2[N:27]([C@H:35]3[CH2:40][CH2:39][C@@H:38]([N:41]4[CH2:42][CH2:43][N:44]([CH3:47])[CH2:45][CH2:46]4)[CH2:37][CH2:36]3)[N:26]=[C:25]([C:12]3[CH:11]=[CH:10][C:9]([C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[O:8])=[CH:14][CH:13]=3)[C:33]=12

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 444266Maleic AcidHCID 12158596Phenyl[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanoneHCID 178481014HCID 178481014, compound

Product 1

HCID 178480960HCID 178480960, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of phenyl[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-methanone (Intermediate AL) (0.241 g, 0.00078 mol), cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AC) (0.30 g, 0.00068 mol), tetrakis(triphenyl-phosphine)palladium (0.047 g, 0.000041 mol) and sodium carbonate (0.18 g, 0.0017 mol) was heated in a mixture of ethylene glycol dimethyl ether (10 mL) and water (5 mL) at 80° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under the reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate, the organic layer separated and the aqueous layer further extracted with ethyl acetate twice. The combined organic extracts were dried over magnesium sulfate. The solvents were evaporated under the reduced pressure to leave a tan solid which was purified by flash column chromatography on silica using dichloromethane/triethylamine/methanol (95:4:1) as a mobile phase to give cis-{4-[4-amino-1-(4-(4-methylpiperazino)cyclohexy)]-1H-pyrazolo[3,4-d]pyrimidin-3-yl-]-phenyl}(phenyl)methanone as a white solid (0.195 g, 0.0004 mol). It was dissolved in refluxing ethanol (17 mL) and a preheated solution of maleic acid (0.137 g, 0.0018 mol) was added. The mixture was refluxed for 10 min, cooled to ambient temperature and the precipitate collected by filtration, washed with ethyl acetate and dried to give cis-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)(phenyl)methanone dimaletate as a white solid (0.221 g, 0.0003 mol): 1H NMR (DMSO-d6, 400 MHz) 8.28 (s, 1H), 7.90 (d, 2H), 7.83 (m, 4H), 7.73 (t, 1H), 7.61 (m, 2H), 6.15 (s, 4H), 4.88 (m, 1H), 3.1 (br, 9H), 2.71 (s, 3H), 2.28 (m, 2H), 2.07 (m, 2H), 1.74 (m, 4H); RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 12.63 min. MS: MH+ 496.

Workup

  1. customsolvents were removed under the reduced pressure
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate
  3. customthe organic layer separated
  4. extractionthe aqueous layer further extracted with ethyl acetate twice
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. customThe solvents were evaporated under the reduced pressure
  7. customto leave a tan solid which
  8. customwas purified by flash column chromatography on silica
  9. customto give cis-{4-[4-amino-1-(4-(4-methylpiperazino)cyclohexy)]-1H-pyrazolo[3,4-d]pyrimidin-3-yl-]-phenyl}(phenyl)methanone as a white solid (0.195 g, 0.0004 mol)
  10. dissolutionIt was dissolved
  11. temperatureThe mixture was refluxed for 10 min
  12. temperaturecooled to ambient temperature
  13. filtrationthe precipitate collected by filtration
  14. washwashed with ethyl acetate
  15. customdried

Sources & evidence

ORD record
ord-6484a8f972cb430b9ba190365d71cfff
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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