Formaldehyde → HCID 10114835, compound

HRID 2180133Notes

Reaction equation

HRID 2180133 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[N:14][CH:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:32])[NH:6]2.[C:33]([O-])(=O)C.[Na+].C=O.[BH4-].[Na+].C(O)(=O)C.C(O)(=O)C.C(O)(=O)C>C(Cl)Cl.CO.C(O)(=O)C>[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH:26]4[CH2:31][CH2:30][N:29]([CH3:33])[CH2:28][CH2:27]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[N:14][CH:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:32])[NH:6]2

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 517045Sodium AcetateHCID 10296729HCID 10296729, compoundHCID 131724855Sodium borohydride triacetate

Product 1

HCID 10114835HCID 10114835, compoundYield 53.7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(piperidin-4-ylmethoxy)cinnoline (170 mg, 0.31 mmol), (prepared as described in Example 6), in methylene chloride (6 ml) and methanol (3 ml) was added a solution of sodium acetate (25 mg, 0.31 mmol). Acetic acid (22 ml) and formaldehyde (37%) (50 ml) were added. The mixture was stirred for 5 minutes and triacetate sodium borohydride (100 mg, 0.46 mmol) was added in portions. The mixture was stirred at ambient temperature for 1 hour. The volatiles were removed under vacuum and the residue was dissolved in water and the pH was adjusted to 10 with 2N aqueous sodium hydroxide. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was triturated under diethyl ether, filtered, washed with ether and dried under vacuum to give 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)cinnoline (75 mg, 43%).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 1 hour
  2. customThe volatiles were removed under vacuum
  3. dissolutionthe residue was dissolved in water
  4. extractionThe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was triturated under diethyl ether
  9. filtrationfiltered
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-973ea33ee2734bd9bb586af63210b8af
Source dataset
uspto-grants-2005_05
Patent number
US06887874B2

Reaction notes

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