Toluene → 6-(Difluoro(6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo(4,3-b)pyridazin-3-yl)methyl)quinoline

HRID 469196Notes

Reaction equation

[F:1][C:2]([C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2)([F:19])[C:3]([N:5]1[N:6]=[C:7]([C:13]2[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=2)[CH:8]=[CH:9]/[C:10]/1=[N:11]\[NH2:12])=O.COCC(O)C.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O>[F:1][C:2]([F:19])([C:3]1[N:5]2[N:6]=[C:7]([C:13]3[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=3)[CH:8]=[CH:9][C:10]2=[N:11][N:12]=1)[C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2

Participants

Conditions

Temperature: 105 °C

Procedure

The crude 6-{1,1-difluoro-2-[(6E)-6-hydrazono-3-(1-methyl-1H-pyrazol-4-yl)pyridazin-1(6H)-yl]-2-oxoethyl}quinoline from step 3 above (3.67 mmol) was brought in a reaction balloon under argon. 36 mL of 1-methoxy-2-propanol was added and the mixture was stirred at 105° C. for 1 h. Then the reaction mixture was brought to gentle reflux for one additional hour (108° C.). The reaction mixture was allowed to cool to room temperature and poured out in a solution of 10 g of sodium carbonate in 100 mL of water. 100 mL toluene was added and the layers were separated. The water layer was extracted with toluene (100 mL). The combined organic layers were washed with water and evaporated, yielding 700 mg of compound (I) (1.86 mmol; 51%).

Workup

temperatureto gentle reflux for one additional hour (108° C.)
temperatureto cool to room temperature
customthe layers were separated
extractionThe water layer was extracted with toluene (100 mL)
washThe combined organic layers were washed with water
customevaporated

Sources & evidence

ORD record: ord-6718632cb75f4e2a91d090287ebc7bbd
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629144B2

Reaction notes

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