Ammonium formate → 4-[2-(4-Fluorophenyl)-6-(hexahydropyrrolo[3,4-c]pyrrol-2-yl)-7,8-dimethylimidazo[1,2-b]pyridazin-3-yl]pyrid-2-ylamine

HRID 80727Notes

Reaction equation

HRID 80727 reaction equation
C([N:8]1[CH2:12][CH:11]2[CH2:13][N:14]([C:16]3[C:17]([CH3:40])=[C:18]([CH3:39])[C:19]4[N:20]([C:22]([C:32]5[CH:37]=[CH:36][N:35]=[C:34]([NH2:38])[CH:33]=5)=[C:23]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)[N:24]=4)[N:21]=3)[CH2:15][CH:10]2[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[Pd]>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:23]2[N:24]=[C:19]3[C:18]([CH3:39])=[C:17]([CH3:40])[C:16]([N:14]4[CH2:13][CH:11]5[CH:10]([CH2:9][NH:8][CH2:12]5)[CH2:15]4)=[N:21][N:20]3[C:22]=2[C:32]2[CH:37]=[CH:36][N:35]=[C:34]([NH2:38])[CH:33]=2)=[CH:26][CH:27]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 594069584-[6-(5-Benzylhexahydropyrrolo[3,4-c]pyrrol-2-yl)-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazin-3-yl]pyrid-2-ylamine

Product 1

HCID 594069684-[2-(4-Fluorophenyl)-6-(hexahydropyrrolo[3,4-c]pyrrol-2-yl)-7,8-dimethylimidazo[1,2-b]pyridazin-3-yl]pyrid-2-ylamine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 2.30 g (4.3 mmol) of 4-[6-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2-yl)-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazin-3-yl]pyrid-2-ylamine in 150 mL of methanol are added 4 g (64 mmol) of ammonium formate and 1 g of 10% palladium-on-charcoal containing 50% water. The mixture is stirred at reflux for 2 hours and the solvent is then removed under reduced pressure. The residue is taken up in water and the resulting aqueous phase is basified using aqueous 1N sodium hydroxide. The product is extracted with chloroform, the organic phase is washed with water, dried over sodium sulfate and filtered, and the solvent is evaporated off to give an orange-colored oil. After purification by chromatography on a column of silica gel, eluting with a mixture of dichloromethane, methanol and aqueous ammonia (87:13:1.3), 1.23 g of a white powder are obtained after crystallization from ether and drying under reduced pressure.

Workup

  1. temperatureat reflux for 2 hours
  2. customthe solvent is then removed under reduced pressure
  3. extractionThe product is extracted with chloroform
  4. washthe organic phase is washed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent is evaporated off
  8. customto give an orange-colored oil
  9. customAfter purification by chromatography on a column of silica gel
  10. washeluting with a mixture of dichloromethane, methanol and aqueous ammonia (87:13:1.3), 1.23 g of a white powder
  11. customare obtained
  12. customafter crystallization from ether
  13. customdrying under reduced pressure

Sources & evidence

ORD record
ord-645cf0411a914e7c913ef969603b1ff9
Source dataset
uspto-grants-2014_09
Patent number
US08846676B2

Reaction notes

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