Sodium Carbonate → HCID 178480963, compound

HRID 432423Notes

Reaction equation

HRID 432423 reaction equation
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.[CH:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)=[O:26].C(=O)([O-])[O-].[Na+].[Na+].B([O-])[O-]>COCCOC.O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:30]3[CH:31]=[CH:32][C:27]([CH:25]=[O:26])=[CH:28][CH:29]=3)[C:10]=12

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 178481014HCID 178481014, compoundHCID 178514824HCID 178514824, compound

Product 1

HCID 178480963HCID 178480963, compoundYield 44.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (5.0 g, 11.33 mmol), 4-formylphenyl boronic acid (2.55 g, 16.98 mmol), palladium tetrakistriphenylphosphine (0.47 g, 0.4 mmol), and sodium carbonate (3.002 g, 28.32 mmol) in ethylene glycol dimethylether (170 mL) and water (30 mL) was heated at 80° C. for 18 h. Additional boronate (1.567 equiv.) and catalyst (0.0135 equiv.) were added and the reaction continued for a further 40 h. The reaction was cooled to ambient temperature and concentrated in vacuo. The residues were partitioned between ethyl acetate (300 mL) and water (200 mL). The resulting precipitate was collected by filtration and dried on the lyophiliser to afford cis-4-{4-Amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzaldehyde as a light brown solid (2.1 g, 43%); RP-HPLC 7.003 min, 98% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 nm; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); 1H NMR (DMSO-d6, 400 MHz) δ 1.60 (2H, br t), 1.72 (2H, m), 2.06 (2H, m), 2.17 (3H, s), 2.27 (3H, m), 2.35-2.50 (6H, m), 3.39 (2H, m), 4.84 (1H, m), 7.88 (2H, d), 8.07 (2H, d), 8.26 (1H, s), and 10.11 (1H, s)

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residues were partitioned between ethyl acetate (300 mL) and water (200 mL)
  4. filtrationThe resulting precipitate was collected by filtration
  5. customdried on the lyophiliser

Sources & evidence

ORD record
ord-69ccd35a3752414dabda5bf534f735bf
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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