1-Propanol → 6-(4-(3-((2-hydroxy-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propyl)amino)propionamido)phenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone

HRID 1906672Notes

Reaction equation

HRID 1906672 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][OH:17])=[CH:11][C:10]=1C)C1C=CC=CC=1.Br[CH2:20][CH2:21][C:22]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]([CH3:38])[CH2:33][C:34](=[O:37])[NH:35][N:36]=2)=[CH:27][CH:26]=1)=[O:23].[CH2:39]([N:41](CC)CC)C.Cl[CH2:47]Cl.[CH3:49][OH:50].[CH2:51](O)[CH2:52][CH3:53]>>[OH:50][CH:49]([CH2:1][O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][O:17][CH2:53][CH:52]2[CH2:51][CH2:47]2)=[CH:13][CH:14]=1)[CH2:39][NH:41][CH2:20][CH2:21][C:22]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]([CH3:38])[CH2:33][C:34](=[O:37])[NH:35][N:36]=2)=[CH:27][CH:26]=1)=[O:23]

Participants

6

Reactant 5

HCID 10311-PropanolHCID 8471TriethylamineHCID 140033506-[4-(3-bromopropionamido)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinoneHCID 20211972HCID 20211972, compoundHCID 21226129Dichloromethane methanol

Product 1

HCID 1833506-(4-(3-((2-hydroxy-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propyl)amino)propionamido)phenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone

Procedure

Part of the product from (i) (48 g), 6-[4-(3-bromopropionamido)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone (60 g) and triethylamine (36 g) were stirred under reflux in n-propanol (700 ml) for 18 hours. The reaction mixture was cooled and evaporated under reduced pressure to afford an oil. This oil was subjected to column chromatography on silica using dichloromethane/methanol (gradient elution 100:0 to 100:5). The desired fractions were combined and purified on another silica column (eluting with ethyl acetate/methanol/ammonia 100:20:0.5). The desired fractions were combined and evaporated under reduced pressure to form the title compound (30 g). Part of this was converted to the methanesulphonate salt as in Example 4.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customevaporated under reduced pressure
  3. customto afford an oil
  4. custompurified on another silica column (eluting with ethyl acetate/methanol/ammonia 100:20:0.5)
  5. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-798106d1d0e040ecbdae4dd5a4b6d5b7
Source dataset
uspto-grants-1987_03
Patent number
US04652563

Reaction notes

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