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

HRID 1921637Notes

Reaction equation

Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)=[CH:6][CH:7]=1.[F:14][C:15]([F:30])([C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2)[C:16]([NH:18][NH2:19])=O.CCOC(C)=O.C([O-])([O-])=O.[K+].[K+]>C(O)CCC>[F:30][C:15]([F:14])([C:16]1[N:3]2[N:4]=[C:5]([C:8]3[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=3)[CH:6]=[CH:7][C:2]2=[N:19][N:18]=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: 130 °C

Procedure

A mixture of 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)-pyridazine (step d) (4.57 g, 23.6 mmol) and difluoro-quinolin-6-yl-acetic acid hydrazide (step c) (5.60 g, 23.6 mmol) in n-butanol (125 mL) was heated to 130° C. overnight. The mixture was cooled to room temperature, followed by aqueous work up using AcOEt and a solution of K2CO3. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography (first chromatography: CH2Cl2 100% and CH2Cl2/MeOH: 88/12 followed by another column with toluene/iPrOH/NH4OH: 85/15/2) to give the title compound (5.5 g, 62%). M.p=199.7° C.

Workup

temperatureThe mixture was cooled to room temperature
dry with materialThe organic layer was dried (MgSO4)
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography (first chromatography

Sources & evidence

ORD record: ord-dc1b0920ca0f40ddb553c589cc9ce157
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173654B2

Reaction notes

Loading…