Hydrogen Bromide → TAS-103 free base

HRID 3156Notes

Reaction equation

HRID 3156 reaction equation
[CH3:1][N:2]([CH2:4][CH2:5][NH:6][C:7]1[C:16]2[C:17](=[O:24])[C:18]3[C:23]([C:15]=2[C:14]2[C:9](=[CH:10][C:11]([O:25]C)=[CH:12][CH:13]=2)[N:8]=1)=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH3:3].Br>C(O)(=O)C>[CH3:3][N:2]([CH2:4][CH2:5][NH:6][C:7]1[C:16]2[C:17](=[O:24])[C:18]3[C:23]([C:15]=2[C:14]2[C:9](=[CH:10][C:11]([OH:25])=[CH:12][CH:13]=2)[N:8]=1)=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH3:1]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 223716586-(((dimethylamino)ethyl)amino)-3-methoxy-7H-indeno[2,1-c]quinoline-7-on

Product 1

HCID 135413533TAS-103 free baseYield 73.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 6-(((dimethylamino)ethyl)amino)-3-methoxy-7H-indeno[2,1-c]quinoline-7-on obtained in example 1 (3 g, 8.6 mmol) in acetic acid (40 ml) was added 47% aqueous hydrobromic acid (40 ml), and the mixture was refluxed with heat for 60 hours. The reaction mixture was distilled to dryness. To the residue was added water and the solution was adjusted to a pH of about 8 with aqueous ammonia, and subsequently extracted with chloroform. The chloroform layer was dried over magnesium sulfate and evaporated. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:water=8:3:1(v/v/v)) and crystallized from cyclohexane to give 2.1 g (yield: 73.0%) of title compound. The physicochemical properties thereof are shown in table 1.

Workup

  1. temperaturethe mixture was refluxed
  2. temperaturewith heat for 60 hours
  3. distillationThe reaction mixture was distilled to dryness
  4. additionTo the residue was added water
  5. extractionsubsequently extracted with chloroform
  6. dry with materialThe chloroform layer was dried over magnesium sulfate
  7. customevaporated
  8. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:water=8:3:1(v/v/v)) and
  9. customcrystallized from cyclohexane

Sources & evidence

ORD record
ord-7a2a319b1424424183bfefb01280793f
Source dataset
uspto-grants-1998_03
Patent number
US05733918

Reaction notes

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