Sodium Hydroxide → tert-butyl 9-[2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]-2,9-diazaspiro[5.5]undecane-2-carboxylate

HRID 1035796Notes

Reaction equation

HRID 1035796 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:33][CH2:32][C:19]5([CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22][CH2:21][CH2:20]5)[CH2:18][CH2:17]4)=[N:12][N:11]3[C:34]=2[C:35]2[CH:40]=[CH:39][N:38]=[C:37]3[N:41](S(C4C=CC(C)=CC=4)(=O)=O)[CH:42]=[CH:43][C:36]=23)=[CH:4][CH:3]=1.[OH-].[Na+]>CO.O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][C:19]5([CH2:24][N:23]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:22][CH2:21][CH2:20]5)[CH2:32][CH2:33]4)=[N:12][N:11]3[C:34]=2[C:35]2[CH:40]=[CH:39][N:38]=[C:37]3[NH:41][CH:42]=[CH:43][C:36]=23)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 58046371HCID 58046371, compound

Product 1

HCID 58046358tert-butyl 9-[2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]-2,9-diazaspiro[5.5]undecane-2-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The tert-butyl 9-{2-(4-fluorophenyl)-3-[1-(4-methylphenylsulphonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]imidazo[1,2-b]pyridazin-6-yl}-2,9-diazaspiro[5.5]undecane-2-carboxylate obtained in step 5.1 is dissolved in 3 ml of a mixture of methanol and tetrahydrofuran (2/1) and is treated using 0.09 ml (0.54 mmol) of a 6N aqueous solution of sodium hydroxide at 60° C. for 1 and a half hours. The solvent is evaporated under reduced pressure and the residue taken up in 3 ml of water. The product is extracted 2 times with 3 ml of dichloromethane. The organic phase is dried over sodium sulphate and the solvent is removed by evaporation under reduced pressure. The residue obtained is then purified by chromatography on a silica gel column (4 g) by eluting with a gradient of dichloromethane, methanol and aqueous ammonia (of 95/5/05 to 90/10/1) in order to give 0.06 g of tert-butyl 9-[2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]-2,9-diazaspiro[5.5]undecane-2-carboxylate after crystallization in 10 ml of acetonitrile, filtration and drying.

Workup

  1. additionis treated
  2. customat 60° C.
  3. customfor 1 and a half hours
  4. customThe solvent is evaporated under reduced pressure
  5. extractionThe product is extracted 2 times with 3 ml of dichloromethane
  6. dry with materialThe organic phase is dried over sodium sulphate
  7. customthe solvent is removed by evaporation under reduced pressure
  8. customThe residue obtained
  9. customis then purified by chromatography on a silica gel column (4 g)
  10. washby eluting with a gradient of dichloromethane, methanol and aqueous ammonia (of 95/5/05 to 90/10/1) in order

Sources & evidence

ORD record
ord-f1d84c779d024991acf4b6d5a494caf8
Source dataset
uspto-grants-2013_10
Patent number
US08546395B2

Reaction notes

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