Dichloromethane → HCID 67280611, compound

HRID 1693296Notes

Reaction equation

HRID 1693296 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[CH:5]1([NH:8][CH:9]2[C:18]3[CH2:17][S:16][N:15]=[C:14]([N:19](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:13]4=[N:34][N:35]([CH2:37][C:38]5[C:43]([CH3:44])=[C:42]([O:45][CH3:46])[C:41]([CH3:47])=[CH:40][N:39]=5)[N:36]=[C:11]([C:12]=34)[CH2:10]2)[CH2:7][CH2:6]1.ClCCl.C(N(CC)CC)C>C(OCC)(=O)C>[NH2:19][C:14]1[C:13]2[C:12]3[C:11](=[N:36][N:35]([CH2:37][C:38]4[C:43]([CH3:44])=[C:42]([O:45][CH3:46])[C:41]([CH3:47])=[CH:40][N:39]=4)[N:34]=2)[CH2:10][CH:9]([N:8]([CH:5]2[CH2:7][CH2:6]2)[C:1](=[O:3])[CH3:2])[C:18]=3[CH2:17][S:16][N:15]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 86641330HCID 86641330, compound

Product 1

HCID 67280611HCID 67280611, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Acetyl chloride (14 μL) was added to a mixture composed of the above di-tert-butyl {8-(cyclopropylamino)-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7,8,9-tetrahydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-4-yl}imidodicarbonate (100 mg), dichloromethane (2 mL) and triethylamine (42 μL) under cooling in an ice bath, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. Dichloromethane (4 mL) and trifluoroacetic acid (1 mL) were added to the resulting residue, and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the resulting residue under ice-cooling, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform-methanol) to obtain the title compound (55 mg, 75%) as an oil.

Workup

  1. temperatureunder cooling in an ice bath
  2. washwashed with a saturated sodium bicarbonate solution
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionDichloromethane (4 mL) and trifluoroacetic acid (1 mL) were added to the resulting residue
  7. stirringthe mixture was stirred at room temperature for one hour
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additionA saturated sodium bicarbonate solution was added to the resulting residue under ice-
  10. temperaturecooling
  11. extractionfollowed by extraction with chloroform
  12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customThe resulting residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-3f4387e9911e4c4c8e49f244401654dd
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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