Sodium Bicarbonate → 6-(Difluoro(6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline

HRID 219262Notes

Reaction equation

[F:1][C:2]([F:17])([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][CH:11]=[CH:10]2)[C:3](OC)=O.[CH3:18][C:19]1[CH:23]=[C:22]([C:24]2[N:29]=[N:28][C:27]([NH:30][NH2:31])=[CH:26][CH:25]=2)[S:21][N:20]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1.CCOC(C)=O>[F:1][C:2]([F:17])([C:3]1[N:28]2[N:29]=[C:24]([C:22]3[S:21][N:20]=[C:19]([CH3:18])[CH:23]=3)[CH:25]=[CH:26][C:27]2=[N:30][N:31]=1)[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][CH:11]=[CH:10]2

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of methyl 2,2-difluoro-2-(quinolin-6-yl)acetate (0.50 g, 2.1 mmol), 1-(6-(3-methylisothiazol-5-yl)pyridazin-3-yl)hydrazine (0.25 g, 1.2 mmol) and p-toluenesulfonic acid monohydrate (0.40 g, 2.1 mmol) in 5 mL of dioxane was heated at 150° C. for 1 hour in a microwave. The mixture was then diluted with 70 mL of EtOAc and 40 mL of satd. NaHCO3 solution. The organic phase was separated and washed with 40 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc to 10% MeOH/EtOAc) to give yellow glass. The product was further purified by a prep-HPLC to give yellow glass. MS (ESI pos. ion) m/z: 395 (MH+). Calc'd exact mass for C19H12F2N6S: 394.

Workup

customThe organic phase was separated
washwashed with 40 mL of brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by a silica gel column chromatography (EtOAc to 10% MeOH/EtOAc)
customto give yellow glass
customThe product was further purified by a prep-HPLC
customto give yellow glass

Sources & evidence

ORD record: ord-9861af7fe49a40e4afe69f55d50e2169
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198448B2

Reaction notes

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