Phosphorus oxychloride → (R)-4-(3-(1-(benzyloxy)ethyl)-8-(4-chlorophenyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-yl)benzonitrile

HRID 1661107Notes

Reaction equation

HRID 1661107 reaction equation
[CH2:1]([O:8][C@H:9]([CH3:48])[C:10]([NH:12][NH:13][C:14]1[C:19]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[C:18]([C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)[C:17](=[O:35])[N:16]([CH2:36][C:37]2[C:38]([CH3:47])=[N:39][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:41][CH:42]=2)[N:15]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH2:1]([O:8][C@@H:9]([C:10]1[N:15]2[N:16]([CH2:36][C:37]3[C:38]([CH3:47])=[N:39][C:40]([C:43]([F:44])([F:45])[F:46])=[CH:41][CH:42]=3)[C:17](=[O:35])[C:18]([C:27]3[CH:28]=[CH:29][C:30]([C:33]#[N:34])=[CH:31][CH:32]=3)=[C:19]([C:20]3[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=3)[C:14]2=[N:13][N:12]=1)[CH3:48])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 67128707(R)-2-(benzyloxy)-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide

Product 1

HCID 67128886(R)-4-(3-(1-(benzyloxy)ethyl)-8-(4-chlorophenyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-yl)benzonitrileYield 44%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a round bottom flask was added (R)-2-(benzyloxy)-N′-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide (70 mg, 0.140 mmol), toluene (3 ml). The reaction was heated to 120° C. POCl3(0.3 ml) was then added and the reaction was stirred at 120° C. for additional 3 hr. The reaction was then cooled to rt and the solution was concentrated. The resulting residue was diluted with EtOAc (30ml). The organic solution was then extracted with saturated NaHCO3 (20 ml), water (20 ml) and saturated NaCl (20 ml). The organic solution was dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (4 g silica gel, 20%-50% EtOAc/Hex) to give product (R) -4-(3-(1-(benzyloxy)ethyl)-8-(4-chlorophenyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-yl)benzonitrile as a white solid (40 mg, 44% yield).

Workup

  1. temperatureThe reaction was then cooled to rt
  2. concentrationthe solution was concentrated
  3. additionThe resulting residue was diluted with EtOAc (30ml)
  4. extractionThe organic solution was then extracted with saturated NaHCO3 (20 ml), water (20 ml) and saturated NaCl (20 ml)
  5. dry with materialThe organic solution was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel column chromatography (4 g silica gel, 20%-50% EtOAc/Hex)

Sources & evidence

ORD record
ord-c79b905aa112496190c9aafdcdf2a78d
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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