Acetonitrile → HCID 67280561, compound

HRID 1693309Notes

Reaction equation

HRID 1693309 reaction equation
[NH2:1][CH2:2][C:3]1[C:12]2[CH2:11][S:10][N:9]=[C:8]([N:13](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:7]3=[N:28][N:29]([CH2:31][C:32]4[C:37]([CH3:38])=[C:36]([O:39][CH3:40])[C:35]([CH3:41])=[CH:34][N:33]=4)[N:30]=[C:5]([C:6]=23)[CH:4]=1.Br[CH2:43][CH2:44][O:45][CH2:46][CH2:47]Br.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O>[CH3:40][O:39][C:36]1[C:35]([CH3:41])=[CH:34][N:33]=[C:32]([CH2:31][N:29]2[N:30]=[C:5]3[CH:4]=[C:3]([CH2:2][N:1]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)[C:12]4[CH2:11][S:10][N:9]=[C:8]([NH2:13])[C:7]([C:6]=43)=[N:28]2)[C:37]=1[CH3:38]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 21521Bis(2-bromoethyl) etherHCID 86641345HCID 86641345, compound

Product 1

HCID 67280561HCID 67280561, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

A mixture composed of di-tert-butyl {8-(aminomethyl)-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7-dihydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-4-yl}imidodicarbonate of Example 112 (20 mg), 90% bis(2-bromoethyl)ether (10 μl), potassium carbonate (9.5 mg) and acetonitrile (0.3 ml) was heated with stirring at 55° C. for 24 hours. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. Dichloromethane (2 ml) and trifluoroacetic acid (0.5 ml) were added to the resulting residue, and the mixture was stirred at room temperature for four hours. The reaction mixture was concentrated under reduced pressure. A saturated sodium bicarbonate solution was placed into the resulting residue, followed by extraction with chloroform. The organic layer was dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was purified by NH silica gel chromatography (chloroform-methanol). The resulting oil was dissolved in dioxane, followed by lyophilization to obtain the title compound (5.6 mg) as an amorphous.

Workup

  1. temperaturewas heated
  2. extractionfollowed by extraction with chloroform
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThen, the filtrate was concentrated under reduced pressure
  6. additionDichloromethane (2 ml) and trifluoroacetic acid (0.5 ml) were added to the resulting residue
  7. stirringthe mixture was stirred at room temperature for four hours
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. extractionfollowed by extraction with chloroform
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationThen, the filtrate was concentrated under reduced pressure
  13. customThe resulting residue was purified by NH silica gel chromatography (chloroform-methanol)
  14. dissolutionThe resulting oil was dissolved in dioxane

Sources & evidence

ORD record
ord-af9240006e304d448498e2a30d90b014
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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