Triethylamine → HCID 58046363, compound

HRID 1035791Notes

Reaction equation

HRID 1035791 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[N:24]([S:27]([C:30]5[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=5)(=[O:29])=[O:28])[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.[CH3:37][C@@H:38]1[CH2:43][NH:42][CH2:41][CH2:40][NH:39]1.C(N(CC)CC)C>C(O)CCCC.Cl>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([N:42]4[CH2:41][CH2:40][NH:39][C@H:38]([CH3:37])[CH2:43]4)=[N:7][N:6]3[C:8]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[N:24]([S:27]([C:30]4[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=4)(=[O:29])=[O:28])[CH:25]=[CH:26][C:19]=23)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 73304342-Methylpiperazine, (R)-HCID 58046364HCID 58046364, compound

Product 1

HCID 58046363HCID 58046363, compoundYield 68.8%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 62761-PentanolSolvent

Procedure

A mixture of 0.330 g (0.58 mmol) of 6-chloro-2(4-fluorophenyl)-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine, 0.116 g (1.16 mmol) of (2R)-2-methylpiperazine and 0.08 ml (0.6 mmol) of triethylamine in 5 ml of pentanol is heated under reflux for 24 hours. The reaction medium is diluted with 100 ml of an aqueous solution of hydrochloric acid and the solution is washed with ethyl acetate. The aqueous phase is then basified by addition of aqueous ammonia 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 chestnut brown solid obtained is then purified by chromatography on 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 0.232 g of 2-(4-fluorophenyl)-6-[(3R)-3-methylpiperazin-1-yl]-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine in the form of a yellow powder after drying.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 24 hours
  3. washthe solution is washed with ethyl acetate
  4. additionThe aqueous phase is then basified by addition of aqueous ammonia
  5. extractionthe product is extracted with dichloromethane
  6. customThe organic phase is separated
  7. dry with materialdried over sodium sulphate
  8. customthe solvent is removed by evaporation under reduced pressure
  9. customThe chestnut brown solid obtained
  10. customis then purified by chromatography on a silica gel column (35 g)
  11. washby eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order

Sources & evidence

ORD record
ord-1294542e9a2f40a888310ef504b8f1e5
Source dataset
uspto-grants-2013_10
Patent number
US08546395B2

Reaction notes

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