Sodium Carbonate → Pyrazolo[3,4-d]pyrimidine 3

HRID 897454Notes

Reaction equation

HRID 897454 reaction equation
[C:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11](B3OC(C)(C)C(C)(C)O3)=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:24]1[C:32]2[C:27](=[N:28][CH:29]=[N:30][C:31]=2[NH2:33])[N:26]([C@H:34]2[CH2:39][CH2:38][C@@H:37]([N:40]3[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]3)[CH2:36][CH2:35]2)[N:25]=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>[NH:7]([C:8]1[CH:9]=[CH:10][C:11]([C:24]2[C:32]3[C:27](=[N:28][CH:29]=[N:30][C:31]=3[NH2:33])[N:26]([CH:34]3[CH2:35][CH2:36][CH:37]([N:40]4[CH2:41][CH2:42][N:43]([CH3:46])[CH2:44][CH2:45]4)[CH2:38][CH2:39]3)[N:25]=2)=[CH:12][CH:13]=1)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 22347219N-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)anilineHCID 178481014HCID 178481014, compound

Product 1

HCID 6539954Pyrazolo[3,4-d]pyrimidine 3Yield 76.3%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of N-phenyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (Intermediate AE) (0.33 g, 0.0011 mol), cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AC) (0.43 g, 0.00097 mol), tetrakis(triphenylphosphine)palladium (0.0067 g, 0.000058 mol) and sodium carbonate (0.26 g, 0.0024 mol) was heated in a mixture of ethylene glycol dimethyl ether (16 mL) and water (8 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 reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (50 mL), the organic layer separated and the aqueous layer further extracted with ethyl acetate twice. The combined organic extracts were dried over magnesium sulfate and evaporated under reduced pressure to give a tan solid which was purified by flash column chromatography on silica using dichloromethane/triethylamine/methanol (92:7:1) as a mobile phase to give 3-(4-anilinophenyl)-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.400 g, 0.00074 mol). It was dissolved at reflux in ethanol (17 mL) and a preheated solution of maleic acid (0.342 g, 0.003 mol) in ethanol (8 mL) 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-3-(4-anilinophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine trimaleate (0.44 g, 0.00053 mol) 1H NMR (DMSO-d6, 400 MHz) 8.45 (s, 1H), 8.23 (s, 1H) 7.52 (d, 2H), 7.28 (m, 2H), 7.20 (m, 4H), 6.89 (t, 1H), 6.19 (s, 6H), 4.83 (m, 1H), 3.1 (br, 9H), 2.72 (s, 3H), 2.28 (m, 2H), 2.07 (m, 2H), 1.74 (m, 4H);

Workup

  1. customsolvents were removed under reduced pressure
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (50 mL)
  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. customevaporated under reduced pressure
  7. customto give a tan solid which
  8. customwas purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-5cd7f7d0775744a3a986e244fb6b225e
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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