Formaldehyde → HCID 86641331, compound

HRID 1693297Notes

Reaction equation

HRID 1693297 reaction equation
[CH:1]1([NH:4][CH:5]2[C:14]3[CH2:13][S:12][N:11]=[C:10]([N:15](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:9]4=[N:30][N:31]([CH2:33][C:34]5[C:39]([CH3:40])=[C:38]([O:41][CH3:42])[C:37]([CH3:43])=[CH:36][N:35]=5)[N:32]=[C:7]([C:8]=34)[CH2:6]2)[CH2:3][CH2:2]1.CO.C=O.[C:48]([BH3-])#N.[Na+]>C(O)(=O)C>[CH:1]1([N:4]([CH3:48])[CH:5]2[C:14]3[CH2:13][S:12][N:11]=[C:10]([NH2:15])[C:9]4=[N:30][N:31]([CH2:33][C:34]5[C:39]([CH3:40])=[C:38]([O:41][CH3:42])[C:37]([CH3:43])=[CH:36][N:35]=5)[N:32]=[C:7]([C:8]=34)[CH2:6]2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 86641330HCID 86641330, compound

Product 1

HCID 86641331HCID 86641331, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture composed of 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 of Example 60 (400 mg), methanol (2 mL), a 35% formalin solution (111 μL), acetic acid (156 μL) and molecular sieves 3A was stirred at room temperature for 40 minutes. Then, sodium cyanoborohydride (163 mg) was added, and the mixture was stirred at room temperature for 14 hours. The molecular sieves were separated off by filtration, and then the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with a saturated sodium bicarbonate solution and then with brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. Dichloromethane (2 mL) and trifluoroacetic acid (2 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 (233 mg, 84%) as an oil.

Workup

  1. customThe molecular sieves were separated off by filtration
  2. customthe solvent was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthe solution was washed with a saturated sodium bicarbonate solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. additionDichloromethane (2 mL) and trifluoroacetic acid (2 mL) were added to the resulting residue
  9. stirringthe mixture was stirred at room temperature for one hour
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. additionA saturated sodium bicarbonate solution was added to the resulting residue under ice-
  12. temperaturecooling
  13. extractionfollowed by extraction with chloroform
  14. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. concentrationthe filtrate was concentrated under reduced pressure
  17. customThe resulting residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-e4278276c8eb4bcca16f661e2e855027
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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