Formaldehyde → HCID 22936906, compound

HRID 1010467Notes

Reaction equation

HRID 1010467 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[OH:16])[N:12]=[CH:11][CH:10]=[C:9]2[O:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][CH3:28])=[O:26])=[C:20]([Cl:29])[CH:19]=1)=[O:5])[CH3:2].Br[CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([C:38](OC(C)(C)C)=O)[CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+].C=O.C([BH3-])#N.[Na+]>CN(C)C=O.C(OCC)(=O)C.CCCCCC.C(O)(=O)C.O>[CH2:1]([NH:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1)[N:12]=[CH:11][CH:10]=[C:9]2[O:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][CH3:28])=[O:26])=[C:20]([Cl:29])[CH:19]=1)=[O:5])[CH3:2]

Participants

11

Reactant 5

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 135829396HCID 135829396, compound

Product 1

HCID 22936906HCID 22936906, compoundYield 57%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

N6-Ethyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-hydroxy-6-quinolinecarboxamide) (80.0 mg, 0.193 mmol), tert-butyl 4-(bromomethyl)-1-piperidinecarboxylate (80.5 mg, 0.289 mmol) and potassium carbonate (33.3 mg, 0.241 mmol) were heated and stirred in dimethylformamide (1 ml) at 60° C. for 15 hours. The reaction solution was distributed between ethyl acetate and water, the organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was distilled off under reduced pressure. The obtained product was stirred in trifluoroacetic acid (1 ml) at room temperature for 1 hour, and then the reaction solution was concentrated under reduced pressure, the residue was dissolved in methanol and triethylamine was added dropwise for neutralization. After distilling off the solvent, the residue was dissolved in a tetrahydrofuran (2 ml)-methanol (2 ml) mixed solvent, and then a 37% formaldehyde aqueous solution (0.360 ml), acetic acid (0.070 ml) and sodium cyanoborohydride (36.3 mg, 0.579 mmol) were added in that order at room temperature and the mixture was stirred for 15 minutes. After adding basic silica gel to the reaction solution and concentrating it, it was subjected to silica gel column chromatography, the target fraction was concentrated under reduced pressure, the obtained crude product was suspended in ethyl acetate, the suspension was diluted with hexane, and the crystals were filtered out, washed with hexane and blow-dried to obtain the title compound (57.5 mg, 0.109 mmol, 57%) as white crystals.

Workup

  1. washthe organic layer was washed with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationthe drying agent was filtered off
  4. distillationthe filtrate was distilled off under reduced pressure
  5. concentrationthe reaction solution was concentrated under reduced pressure
  6. dissolutionthe residue was dissolved in methanol
  7. additiontriethylamine was added dropwise for neutralization
  8. distillationAfter distilling off the solvent
  9. dissolutionthe residue was dissolved in a tetrahydrofuran (2 ml)-methanol (2 ml)
  10. additionmixed solvent
  11. stirringthe mixture was stirred for 15 minutes
  12. additionAfter adding basic silica gel to the reaction solution
  13. concentrationconcentrating it, it
  14. concentrationthe target fraction was concentrated under reduced pressure
  15. customthe obtained crude product
  16. filtrationthe crystals were filtered out
  17. washwashed with hexane
  18. customblow-dried

Sources & evidence

ORD record
ord-908341049fa148f390ed8281ab0f83f1
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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