Sodium Hydroxide → HCID 67280860, compound

HRID 1693303Notes

Reaction equation

HRID 1693303 reaction equation
COC1C=C(OC)C=CC=1[CH2:5][NH:6][CH:7]1[C:16]2[CH2:15][S:14][N:13]=[C:12]([N:17](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:11]3=[N:32][N:33]([CH2:35][C:36]4[C:41]([CH3:42])=[C:40]([O:43][CH3:44])[C:39]([CH3:45])=[CH:38][N:37]=4)[N:34]=[C:9]([C:10]=23)[CH2:8]1.Cl[CH2:53][CH2:54][N:55]=C=O.[OH-:58].[Na+]>ClCCl>[NH2:17][C:12]1[C:11]2[C:10]3[C:9](=[N:34][N:33]([CH2:35][C:36]4[C:41]([CH3:42])=[C:40]([O:43][CH3:44])[C:39]([CH3:45])=[CH:38][N:37]=4)[N:32]=2)[CH2:8][CH:7]([N:6]2[CH2:53][CH2:54][NH:55][C:5]2=[O:58])[C:16]=3[CH2:15][S:14][N:13]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 160352-Chloroethyl isocyanateHCID 86641327HCID 86641327, compound

Product 1

HCID 67280860HCID 67280860, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture composed of di-tert-butyl {8-[(2,4-dimethoxybenzyl)amino]-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 of Example 42 (47 mg), dichloromethane (1 ml) and 2-chloroethyl isocyanate (8 μl) was stirred at room temperature for 12 hours. A 0.1 N sodium hydroxide solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dehydrated dichloromethane (1.5 ml). 1,3-Dimethoxybenzene (16 μl) and trifluoroacetic acid (1.5 ml) was added and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and a 0.1 N sodium hydroxide solution was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. Dimethylformamide (1 ml) and potassium tert-butoxide (15 mg) were added to the resulting residue, and the mixture was stirred at room temperature for two hours. The reaction mixture was separated with water and chloroform. Then, the organic layer was dried over sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (chloroform-methanol) to obtain the title compound (9 mg, 31%) as a solid.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationThen, the filtrate was concentrated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in dehydrated dichloromethane (1.5 ml)
  6. addition1,3-Dimethoxybenzene (16 μl) and trifluoroacetic acid (1.5 ml) was added
  7. stirringthe mixture was stirred at room temperature overnight
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additiona 0.1 N sodium hydroxide solution was added to the resulting residue
  10. extractionfollowed by extraction with ethyl acetate
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationThen, the filtrate was concentrated under reduced pressure
  14. additionDimethylformamide (1 ml) and potassium tert-butoxide (15 mg) were added to the resulting residue
  15. stirringthe mixture was stirred at room temperature for two hours
  16. customThe reaction mixture was separated with water and chloroform
  17. dry with materialThen, the organic layer was dried over sodium sulfate
  18. filtrationfiltered
  19. concentrationthe filtrate was concentrated under reduced pressure
  20. customThe resulting residue was purified by silica gel thin-layer chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-7b1ec658405e48ff8ee90da3b827ec59
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

Loading…