Butyl vinyl ether → HCID 68283075, compound

HRID 1527273Notes

Reaction equation

Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[N:3]=1.[CH2:23]([O:27]C=C)[CH2:24]CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CC#N.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:23]([C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[N:3]=1)(=[O:27])[CH3:24]

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of methyl 3-bromo-1-(2-tert-butoxy-2-oxoethyl)-1H-indazole-6-carboxylate (1.00 g, 2.71 mmol), n-butyl vinylether (1.75 mL, 13.5 mmol), palladium acetate (61 mg, 0.27 mmol), triphenylphosphine (142 mg, 0.54 mmol) and triethylamine (0.45 mL, 3.25 mmol) in dry CH3CN (10 mL) was heated at 100° C. under microwave irradiation for 7 h. Then, the mixture was further heated at 120° C. for 5 h under microwave irradiation. The solvent was evaporated, and the residue was then treated with 4N HCl/dioxane with stirring at RT for 16 h. Volatiles were evaporated and the residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) to give after lyophilization of the pure fractions the title compound. MS (LC-MS): 333 [M+H]+, 355 [M+Na]; tR (HPLC conditions k): 3.83 min.

Workup

customThe solvent was evaporated
additionthe residue was then treated with 4N HCl/dioxane
customVolatiles were evaporated
customthe residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record: ord-a0bf12dd607a481eaa63c49282d3f8dd
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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