Sodium hydride → HCID 178476629, compound

HRID 897787Notes

Reaction equation

HRID 897787 reaction equation
[I-].[CH3:2][S+](C)(C)=[O:4].[H-].[Na+].[NH2:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([C@H:35]3[CH2:40][CH2:39][C@H:38]([N:41]4[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]4)[CH2:37][CH2:36]3)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([N:25]=[CH:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[OH:33])=[C:21]([Cl:34])[CH:20]=3)[C:11]=12>CS(C)=O>[C:28]([OH:33])(=[O:4])[CH3:29].[Cl:34][C:21]1[CH:20]=[C:19]([C:18]2[C:11]3[C:12](=[N:13][CH:14]=[N:15][C:10]=3[NH2:9])[N:16]([C@H:35]3[CH2:36][CH2:37][C@H:38]([N:41]4[CH2:42][CH2:43][N:44]([CH3:47])[CH2:45][CH2:46]4)[CH2:39][CH2:40]3)[N:17]=2)[CH:24]=[CH:23][C:22]=1[NH:25][CH:26]1[CH2:2][O:33][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 178480985HCID 178480985, compound

Product 1

HCID 178476629HCID 178476629, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Salicylaldehyde (0.033 g, 0.000274 mol) and trans-3-(4-amino-3-chlorophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.115 g, 0.000261 mol) were combined in absolute ethanol and stirred at ambient temperature for 48 hours. The reaction mixture was concentrated under reduced pressure and the residue dried overnight to yield trans-2-[(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-chlorophenyl)imino]methylphenol which was used without further purification. Trimethylsulfoxonium iodide (0.110 g, 0.0005 mol) was dissolved in anhydrous dimethylsulfoxide (2 mL) and 60% dispersion of sodium hydride in paraffine (0.02 g, 0005 mol) was added at once. After 10 min., the solution of trans-2-[(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-chlorophenyl)imino]methylphenol in anhydrous dimethylsulfoxide (2 mL) was added and the resulting mixture was stirred at ambient temperature under an atmosphere of nitrogen for 2.5 hours. The solution was poured into ice-cold water (50 mL) and extracted with dichloromethane (2×40 mL). The combined organic extracts were dried with magnesium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1M ammonium acetate over 25 min, 21 mL/min) to yield trans-3-[3-chloro-4-(2,3-dihydrobenzo[b]furan-3-ylamino)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine acetate (0.044 g, 0.000071 mol) as a white solid.

Workup

  1. customwas used without further purification
  2. extractionextracted with dichloromethane (2×40 mL)
  3. dry with materialThe combined organic extracts were dried with magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1M ammonium acetate over 25 min, 21 mL/min)

Sources & evidence

ORD record
ord-a29f45a80b574f6ab1821c26004e1ef0
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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