Formaldehyde → HCID 57917370, compound

HRID 69286Notes

Reaction equation

HRID 69286 reaction equation
CO.[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH3:13])=[CH:6][C:5]=1[CH2:14][C:15]1[N:19]2[N:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[CH:28]=3)[CH:22]=[CH:23][C:18]2=[N:17][CH:16]=1.C=O.[BH3-][C:38]#N.[Na+]>CCOC(C)=O.C(O)(=O)C>[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH3:13])=[CH:6][C:5]=1[CH2:14][C:15]1[N:19]2[N:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:29]4[CH2:34][CH2:33][N:32]([CH3:38])[CH2:31][CH2:30]4)[CH:28]=3)[CH:22]=[CH:23][C:18]2=[N:17][CH:16]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 57917419HCID 57917419, compound

Product 1

HCID 57917370HCID 57917370, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To abs. MeOH (2 mL) stirred at rt were added 3-(6-fluoro-1-methyl-1H-indazol-5-ylmethyl)-6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 282, 79 mg, 0.184 mmol), formaldehyde (0.068 mL, 0.918 mmol) and NaBH3CN (58 mg, 0.918 mmol). The RM was then brought to pH 5-6 with addition of acetic acid and stirred at rt for 2 h. It was then taken into EtOAc and washed with saturated NaHCO3 sol. The organic layer was then washed with brine, dried on Na2SO4, filtered and evaporated. The residue was then purified by preparative HPLC with acetonitrile and water (+0.1% TFA) to afford the title compound (tR 0.85 min (conditions 2), MH+=445).

Workup

  1. washwashed with saturated NaHCO3 sol. The organic layer
  2. washwas then washed with brine
  3. customdried on Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was then purified by preparative HPLC with acetonitrile and water (+0.1% TFA)

Sources & evidence

ORD record
ord-d24494d3d51b4de9992c2080c763e5c7
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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