Cesium fluoride → 1-Methyl-4-(((3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-yl)amino)methyl)piperidin-4-ol

HRID 1483793Notes

Reaction equation

[F-].[Cs+].Cl[C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=3)=[CH:11][N:12]=2)[N:9]=1.[NH2:24][CH2:25][C:26]1([OH:33])[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]1>CS(C)=O>[CH3:32][N:29]1[CH2:30][CH2:31][C:26]([CH2:25][NH:24][C:4]2[CH:5]=[CH:6][C:7]3[N:8]([C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=4)=[CH:11][N:12]=3)[N:9]=2)([OH:33])[CH2:27][CH2:28]1

Participants

Conditions

Temperature: 120 °C

Procedure

CsF (50 mg, 0.33 mmol) was added to the mixture of 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (150 mg, 0.48 mmol) and 4-(aminomethyl)-1-methylpiperidin-4-ol (150 mg, 1.04 mmol) in DMSO (1.5 mL). The mixture was heated to 120° C. over night and partitioned with EtOAc (10 mL) and water (10 mL). The organic layer was washed with brine (8 mL×3), dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by pre-HPLC to give the product 1-methyl-4-(((3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-yl)amino)methyl)piperidin-4-ol (22 mg, 10%)

Workup

custompartitioned with EtOAc (10 mL) and water (10 mL)
washThe organic layer was washed with brine (8 mL×3)
dry with materialdried with Na2SO4
concentrationconcentrated under reduced pressure
customThe residue was purified by pre-HPLC

Sources & evidence

ORD record: ord-86f3a79c95464a90988948515f51df22
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416132B2

Reaction notes

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