Phosphorus oxychloride → HCID 25026888, compound

HRID 1661115Notes

Reaction equation

HRID 1661115 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH:35][NH:36][C:37](=O)[CH2:38][N:39]([CH3:41])[CH3:40])=[N:10][N:11]([CH2:23][C:24]3[C:25]([CH3:34])=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[C:12](=[O:22])[C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[N:10]([C:37]([CH2:38][N:39]([CH3:41])[CH3:40])=[N:36][N:35]=3)[N:11]([CH2:23][C:24]3[C:25]([CH3:34])=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[C:12](=[O:22])[C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 67128795HCID 67128795, compound

Product 1

HCID 25026888HCID 25026888, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a round bottom flask was added N′-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)-2-(dimethylamino)acetohydrazide (25 mg, 0.0446 mmol) and toluene (3 ml). The reaction was stirred at 120° C. for 15 min. Then POCl3 (0.3 ml) was added and the reaction was stirred at 120° C. for additional 40 min. After this time, the solution was cooled to rt and the reaction mixture was concentrated. The residue was partitioned between EtOAc (30 ml) and NaHCO3 (sat, 20 ml). The organic layer was separated and washed with water (10 ml) and saturated NaCl (10 ml). The organic layer was then dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (4 g silica gel) eluting with a gradient of 0-80% EtOAc/CH2Cl2 to give product 4-(8-(4-chlorophenyl)-3-((dimethylamino)methyl)-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 an off white solid (10 mg, 39% yield).

Workup

  1. stirringthe reaction was stirred at 120° C. for additional 40 min
  2. temperatureAfter this time, the solution was cooled to rt
  3. concentrationthe reaction mixture was concentrated
  4. customThe residue was partitioned between EtOAc (30 ml) and NaHCO3 (sat, 20 ml)
  5. customThe organic layer was separated
  6. washwashed with water (10 ml) and saturated NaCl (10 ml)
  7. dry with materialThe organic layer was then dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel column chromatography (4 g silica gel)
  11. washeluting with a gradient of 0-80% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-7c6bbe5a08384499bdd2a6a0a16313a3
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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