Methanol → 6-chloro-2-(4-fluorophenyl)-8-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine

HRID 1035786Notes

Reaction equation

HRID 1035786 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:36])[C:5]2[N:6]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[N:24](S(C5C=CC=CC=5)(=O)=O)[CH:25]=[CH:26][C:19]=34)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.CO.O1CCCC1.[OH-].[Na+]>O>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:36])[C:5]2[N:6]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[NH:24][CH:25]=[CH:26][C:19]=34)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:10]=2)[N:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 468994996-chloro-2-(4-fluorophenyl)-8-methyl-3-[1-(phenylsulphonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]imidazo[1,2-b]pyridazine

Product 1

HCID 468995006-chloro-2-(4-fluorophenyl)-8-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazineYield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Added to a suspension of 0.50 g (0.97 mmol) of 6-chloro-2-(4-fluorophenyl)-8-methyl-3-[1-(phenylsulphonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]imidazo[1,2-b]pyridazine in 10 ml of a mixture of methanol and a few ml of tetrahydrofuran is 0.32 ml (1.9 mmol) of a 6N aqueous solution of sodium hydroxide. The mixture gradually become homogeneous and the reaction is stirred for 30 minutes. The reaction medium is diluted with 100 ml of water and the product is extracted with dichloromethane. The organic phase is separated, dried over sodium sulphate and the solvent is removed by evaporation under reduced pressure. The orange solid obtained is then chromatographed over a silica gel column (35 g) by eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order to give 0.293 g of 6-chloro-2-(4-fluorophenyl)-8-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine in the form of a yellow powder after trituration in isopropyl ether, chilling, filtration and drying.

Workup

  1. extractionthe product is extracted with dichloromethane
  2. customThe organic phase is separated
  3. dry with materialdried over sodium sulphate
  4. customthe solvent is removed by evaporation under reduced pressure
  5. customThe orange solid obtained
  6. customis then chromatographed over a silica gel column (35 g)
  7. washby eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order

Sources & evidence

ORD record
ord-85e6e718ada247c09cf64b80f959646c
Source dataset
uspto-grants-2013_10
Patent number
US08546395B2

Reaction notes

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