Sodium Carbonate Monohydrate → HCID 178480966, compound

HRID 432327Notes

Reaction equation

HRID 432327 reaction equation
[O:1]1[CH2:5][CH:4]([NH:6][C:7]2[CH:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][CH:8]=2)[C:3]2[CH:22]=[CH:23][CH:24]=[CH:25][C:2]1=2.I[C:27]1[C:35]2[C:30](=[N:31][CH:32]=[N:33][C:34]=2[NH2:36])[N:29]([C@H:37]2[CH2:42][CH2:41][C@@H:40]([N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)[CH2:39][CH2:38]2)[N:28]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[O:1]1[CH2:5][CH:4]([NH:6][C:7]2[CH:8]=[CH:9][C:10]([C:27]3[C:35]4[C:30](=[N:31][CH:32]=[N:33][C:34]=4[NH2:36])[N:29]([C@H:37]4[CH2:38][CH2:39][C@@H:40]([N:43]5[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]5)[CH2:41][CH2:42]4)[N:28]=3)=[CH:11][CH:12]=2)[C:3]2[CH:22]=[CH:23][CH:24]=[CH:25][C:2]1=2

Participants

6

Reactant 3

HCID 2735133Sodium Carbonate MonohydrateHCID 22346766N-(2,3-dihydrobenzo[b]furan-3-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amineHCID 178481014HCID 178481014, compound

Product 1

HCID 178480966HCID 178480966, compoundYield 20.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of N-(2,3-dihydrobenzo[b]furan-3-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.080 g, 0.000237 mol), cis-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.087 g, 0.000198 mol), tetrakis-(triphenylphosphine)palladium (0.014 g, 0.000012 mol) and sodium carbonate monohydrate (0.061 g, 0.000495 mol) was heated in a mixture of ethylene glycol dimethyl ether (5 mL) and water (3 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 purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1 M ammonium acetate over 25 min, 21 mL/min). Subsequently, the crude product was dissolved in dichloromethane, loaded onto Trikonex column (7 cm) and eluted with dichloromethane (5 mL). The desired band was cut, the product was extracted with a mixture of dichloromethane/methanol/triethylamine in a ratio of 90:5:5 (10 mL) and the solvents were removed under reduced pressure. The residue was triturated in diethyl ether and the precipitate was collected by filtration and dried to yield cis-3-[4-(2,3-dihydrobenzo[b]furan-3-ylamino)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.021 g, 0.00004 mol) as a white solid.

Workup

  1. customsolvents were removed under the reduced pressure
  2. customThe residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1 M ammonium acetate over 25 min, 21 mL/min)
  3. dissolutionSubsequently, the crude product was dissolved in dichloromethane
  4. washeluted with dichloromethane (5 mL)
  5. extractionthe product was extracted with a mixture of dichloromethane/methanol/triethylamine in a ratio of 90:5:5 (10 mL)
  6. customthe solvents were removed under reduced pressure
  7. customThe residue was triturated in diethyl ether
  8. filtrationthe precipitate was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-9dd83b051cdc41739aeee7d85c7dca3d
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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