Pyrrolidine → 3-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-6-pyrrolidin-1-yl-pyridazine

HRID 548837Notes

Reaction equation

Cl[C:2]1[N:3]=[N:4][C:5]([O:8][CH2:9][C:10]2[C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][O:13][C:14]=2[CH3:15])=[CH:6][CH:7]=1.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:15][C:14]1[O:13][N:12]=[C:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]=1[CH2:9][O:8][C:5]1[N:4]=[N:3][C:2]([N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 3-chloro-6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridazine (300 mg, 1.0 mmol) in toluene (5 mL) was added pyrrolidine (0.10 mL, 1.2 mmol), sodium tert-butoxide (115 mg, 1.2 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1-binaphtalene (19 mg, 0.03 mmol) and tris(dibenzylideneacetone)dipalladium chloroform complex (10 mg, 0.01 mmol). The resulting mixture was heated at 110° C. for 55 min with microwave heating. Then the reaction mixture was concentrated and extracted (ethyl acetate/brine). The organic phase was dried over sodium sulfate, concentrated and chromatographed (SiO2, dichloromethane:methanol=100:0 to 99:1) to afford the title compound as a light yellow oil (80 mg, 24%). MS: m/e=337.5 [M+H]−.

Workup

temperatureheating
concentrationThen the reaction mixture was concentrated
extractionextracted (ethyl acetate/brine)
dry with materialThe organic phase was dried over sodium sulfate
concentrationconcentrated
customchromatographed (SiO2, dichloromethane:methanol=100:0 to 99:1)

Sources & evidence

ORD record: ord-be063daa40a9465d9bee1041d3b087a8
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943619B2

Reaction notes

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