Binap, (A+-)- → N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine

HRID 1483790Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=3)=[CH:9][N:10]=2)[N:7]=1.[NH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(OC(C)(C)C)(C)(C)C.[Na].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[O:27]1[CH2:28][CH2:29][CH:24]([CH2:23][NH:22][C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=4)=[CH:9][N:10]=3)[N:7]=2)[CH2:25][CH2:26]1

Participants

Conditions

Temperature: 100 °C

Procedure

Compound 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (0.2 g, 0.638 mmol), 4-aminomethyltetrahydropyran (0.145 g, 0.956 mmol), Sodium tertiarybutyloxide (0.172 g, 1.785 mmol), rac-BINAP (0.024 g, 0.038 mmol) and Pd2(dba)3 (0.018 g, 0.019 mmol) were combined in a 20 ml vial. Toluene (5 mL) was added and nitrogen was bubbled through the mixture for 5 minutes. The reaction mixture was then heated to 100° C. overnight. Silica gel was added to the reaction mixture and the solvent stripped off. The product was isolated via column chromatography (hexanes:EtOAc) with the Compound N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine eluting at 100% EtOAc.

Workup

customnitrogen was bubbled through the mixture for 5 minutes
additionSilica gel was added to the reaction mixture

Sources & evidence

ORD record: ord-341c11926c2749488bee00a423c91bb1
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416132B2

Reaction notes

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