Formaldehyde → HCID 57917280, compound

HRID 69261Notes

Reaction equation

HRID 69261 reaction equation
[F:1][C:2]1[C:11]([CH2:12][C:13]2[N:17]3[N:18]=[C:19]([C:22]4[CH:23]=[N:24][N:25]([CH:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)[CH:26]=4)[CH:20]=[CH:21][C:16]3=[N:15][CH:14]=2)=[C:10]([F:33])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C=O.[C:36]([BH3-])#N.[Na+].O>CO>[F:1][C:2]1[C:11]([CH2:12][C:13]2[N:17]3[N:18]=[C:19]([C:22]4[CH:23]=[N:24][N:25]([CH:27]5[CH2:32][CH2:31][N:30]([CH3:36])[CH2:29][CH2:28]5)[CH:26]=4)[CH:20]=[CH:21][C:16]3=[N:15][CH:14]=2)=[C:10]([F:33])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 579174245,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

Product 1

HCID 57917280HCID 57917280, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 245, 40 mg, 0.090 mmol) was dissolved in MeOH (1.5 mL) with formaldehyde (0.034 mL, 0.449 mmol) and sodium cyanoborohydride (33.2 mg, 0.449 mmol). The RM was stirred at rt for 2 h. Water was added and it was extracted with EtOAc twice. Combined organic layers were washed with brine and dried over Na2SO4, filtered and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt of the title compound (tR 0.8 min (conditions 2), MH+=460).

Workup

  1. extractionit was extracted with EtOAc twice
  2. washCombined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed
  6. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  7. dissolutionThe residue was dissolved in MeOH
  8. customto remove the TFA salt
  9. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-65ea0d25112d4effa3b15e7695086629
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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