Acetonitrile → (R)-4-(8-(4-chlorophenyl)-3-(1-hydroxyethyl)-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 1661108Notes

Reaction equation

HRID 1661108 reaction equation
C([O:8][C@@H:9]([C:11]1[N:15]2[N:16]([CH2:36][C:37]3[C:38]([CH3:47])=[N:39][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:41][CH:42]=3)[C:17](=[O:35])[C:18]([C:27]3[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=3)=[C:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[C:14]2=[N:13][N:12]=1)[CH3:10])C1C=CC=CC=1.CC#N.[Si](I)(C)(C)C>CCOC(C)=O>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([C:19]2[C:14]3[N:15]([C:11]([C@H:9]([OH:8])[CH3:10])=[N:12][N:13]=3)[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]=2[C:27]2[CH:28]=[CH:29][C:30]([C:31]#[N:32])=[CH:33][CH:34]=2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 85247Trimethylsilyl iodideHCID 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)benzonitrile

Product 1

HCID 59177924(R)-4-(8-(4-chlorophenyl)-3-(1-hydroxyethyl)-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 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a round bottom flask was added (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 (40 mg, 0.061 mmol), CH3CN (2 ml) and TMSI (244 mg, 1.22 mmol). The reaction was stirred at 60° C. under argon for 20 hr. After this time, the solution was cooled to rt and diluted with EtOAc (50 ml). The resulting organic solution was extracted with water (20 ml), 10% NaHSO3 (20 ml) and saturated NaCl (20 ml). The organic layer was dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (8 g silica gel) eluting with a gradient of 20% to 80% EtOAc/Hex to give the product (R)-4-(8-(4-chlorophenyl)-3-(1-hydroxyethyl)-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 (15 mg, 44% yield).

Workup

  1. temperatureAfter this time, the solution was cooled to rt
  2. extractionThe resulting organic solution was extracted with water (20 ml), 10% NaHSO3 (20 ml) and saturated NaCl (20 ml)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel column chromatography (8 g silica gel)
  7. washeluting with a gradient of 20% to 80% EtOAc/Hex

Sources & evidence

ORD record
ord-25e86478644f42c69057a6c950412dfa
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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