Acetic Acid → HCID 86759301, compound

HRID 897524Notes

Reaction equation

HRID 897524 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:27][C:26](=O)[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:54]([OH:61])(=[O:60])/[CH:55]=[CH:56]\[C:57]([OH:59])=[O:58]>ClCCCl.C(O)C>[C:54]([O-:61])(=[O:60])/[CH:55]=[CH:56]\[C:57]([O-:59])=[O:58].[C:54]([O-:61])(=[O:60])/[CH:55]=[CH:56]\[C:57]([O-:59])=[O:58].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:27][CH:26]([NH+:33]4[CH2:34][CH2:35][NH+:30]([CH3:29])[CH2:31][CH2:32]4)[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:15][CH:16]=3)[C:3]=12.[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:27][CH:26]([NH+:33]4[CH2:34][CH2:35][NH+:30]([CH3:29])[CH2:31][CH2:32]4)[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:15][CH:16]=3)[C:3]=12

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 444266Maleic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 22346823HCID 22346823, compound

Product 1

HCID 86759301HCID 86759301, compoundYield 0.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolvent2×

Conditions

Temperature
40 °C

Procedure

A mixture of 3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclobutanone (0.300 g, 0.00081 mol), N-methylpiperazine (0.243 g, 0.00242 mol) and acetic acid (0.146 g, 0.00242 mol) in 1,2-dichloroethane (20 ml) was stirred for twenty min at 40° C. and sodium triacetoxyborohydride (0.223 g, 0.00105 mol) was added in three portions over one hour. The mixture was stirred for eighteen hours at 40° C. The solvent was removed under reduced pressure and the residue partitioned between aqueous saturated sodium bicarbonate solution (30 ml) and chloroform (15 ml). The organic layer was separated and the aqueous layer was further extracted with chloroform three times (15 ml each). The combined organic extracts were dried over magnesium sulfate and the solvent removed under reduced pressure to yield yellow oil that was purified by flash chromatography on silica gel using dichloromethane/methanol (97:3) as a mobile phase. The solvent was removed in vacuo and the residue (0.120 g, 0.000263 mol) was dissolved in absolute ethanol (10 mL). A solution of maleic acid (0.122 g, 0.001053 mol) in absolute ethanol (5 mL) was added and the mixture was stirred at reflux for fifteen minutes. The solution was cooled to room temperature and the precipitate was filtered, washing with absolute ethanol (3×5 mL). The solvent was removed in vacuo to give 1-{3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]cyclobutyl}-4-methylhexahydropyrazinediium dimaleate (0.181 g, 0.000397 mmol) as a white solid.

Workup

  1. stirringThe mixture was stirred for eighteen hours at 40° C
  2. customThe solvent was removed under reduced pressure
  3. customthe residue partitioned between aqueous saturated sodium bicarbonate solution (30 ml) and chloroform (15 ml)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was further extracted with chloroform three times (15 ml each)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. customthe solvent removed under reduced pressure
  8. customto yield yellow oil that
  9. customwas purified by flash chromatography on silica gel
  10. customThe solvent was removed in vacuo
  11. stirringthe mixture was stirred
  12. temperatureat reflux for fifteen minutes
  13. temperatureThe solution was cooled to room temperature
  14. filtrationthe precipitate was filtered
  15. washwashing with absolute ethanol (3×5 mL)
  16. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-f6c5fbe9a37f416c8ae7cc8768c1ebb8
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

Loading…