1-(2-Hydroxyethyl)piperazine → HCID 58046369, compound

HRID 1035793Notes

Reaction equation

HRID 1035793 reaction equation
Cl[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:27]([C:30]5[CH:35]=[CH:34][CH:33]=[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.[OH:37][CH2:38][CH2:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]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[C:4]([CH3:36])=[CH:3][C:2]([N:43]4[CH2:44][CH2:45][N:40]([CH2:39][CH2:38][OH:37])[CH2:41][CH2:42]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][CH:33]=[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 76771-(2-Hydroxyethyl)piperazineHCID 8471TriethylamineHCID 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 58046369HCID 58046369, compoundYield 35.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 62761-PentanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 0.530 g (1.02 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, prepared according to the method described in step 1.4 from Example 1, 0.266 g (2.05 mmol) of 1-(2-hydroxyethyl)piperazine (CAS 103-76-4) and 0.14 ml (1.0 mmol) of triethylamine in 5 ml of pentanol is stirred for 2 days at 150° C. The reaction medium is diluted with 20 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 brown oil obtained is then purified by chromatography on a silica gel column (40 g) by eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order to give 0.220 g of 2-{4-[2-(4-fluorophenyl)-8-methyl-3-{1-[phenylsulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazin-6-yl]piperazin-1-yl}ethanol in the form of an amorphous powder which is used in the following step.

Workup

  1. customprepared
  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 brown oil obtained
  9. customis then purified by chromatography on a silica gel column (40 g)
  10. washby eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order

Sources & evidence

ORD record
ord-918e66b490ba4866ae1f0a6c46acba92
Source dataset
uspto-grants-2013_10
Patent number
US08546395B2

Reaction notes

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