Triethylamine → 2-methyl-6-[(3R)-3-methylpiperazin-1-yl]-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine

HRID 1035789Notes

Reaction equation

HRID 1035789 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[N:18]([S:21]([C:24]5[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=5)(=[O:23])=[O:22])[CH:19]=[CH:20][C:13]=34)=[C:9]([CH3:11])[N:10]=2)[N:7]=1.[CH3:31][C@@H:32]1[CH2:37][NH:36][CH2:35][CH2:34][NH:33]1.C(N(CC)CC)C>C(O)CCCC.Cl>[CH3:11][C:9]1[N:10]=[C:5]2[CH:4]=[CH:3][C:2]([N:36]3[CH2:35][CH2:34][NH:33][C@H:32]([CH3:31])[CH2:37]3)=[N:7][N:6]2[C:8]=1[C:12]1[CH:17]=[CH:16][N:15]=[C:14]2[N:18]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:19]=[CH:20][C:13]=12

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 73304342-Methylpiperazine, (R)-HCID 580463686-chloro-2-methyl-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine

Product 1

HCID 580463652-methyl-6-[(3R)-3-methylpiperazin-1-yl]-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazineYield 60.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 62761-PentanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 0.325 g (0.97 mmol) of 6-chloro-2-methyl-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine, 0.15 g (1.5 mmol) of (2R)-2-methylpiperazine and 0.10 ml (0.74 mmol) of triethylamine in 5 ml of pentanol is heated under reflux for 3 days at 150° C. The reaction medium is diluted with 100 ml of a 1N 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 oil obtained is then chromatographed over a silica gel column (35 g) by eluting with a mixture of dichloromethane, methanol and aqueous ammonia (90/10/1) in order to give 0.293 g of 2-methyl-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 oil after drying.

Workup

  1. temperatureis heated
  2. washthe solution is washed with ethyl acetate
  3. additionThe aqueous phase is then basified by addition of aqueous ammonia
  4. extractionthe product is extracted with dichloromethane
  5. customThe organic phase is separated
  6. dry with materialdried over sodium sulphate
  7. customthe solvent is removed by evaporation under reduced pressure
  8. customThe chestnut brown oil obtained
  9. customis then chromatographed over a silica gel column (35 g)
  10. washby eluting with a mixture of dichloromethane, methanol and aqueous ammonia (90/10/1) in order

Sources & evidence

ORD record
ord-24c3f7ca65b246c59b0e225811c20d4c
Source dataset
uspto-grants-2013_10
Patent number
US08546395B2

Reaction notes

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