Lithium Hexamethyldisilazide → Ethyl 3-amino-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)furo[2,3-b]pyridine-2-carboxylate

HRID 8786Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:29]#[N:30])[C:11]([O:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[NH2:30][C:29]1[C:10]2[C:11](=[N:12][C:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=3[Cl:21])=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH:9]=2)[O:22][C:23]=1[C:24]([O:26][CH2:27][CH3:28])=[O:25]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of the product from Step B (0.130 g; 0.282 mmol) in THF (3 mL) cooled to 0° C. was treated with 1 M solution of lithium bis(trimethylsilyl)amide in THF (0.85 mL; 0.85 mmol) and stirred at 0° C. under nitrogen for 30 minutes. The reaction mixture was quenched at 0° C. with 10% aqueous NaHSO4 solution. The reaction mixture was partitioned between ethyl acetate and 10% NaHSO4 aqueous solution. The organic layer was washed twice with saturated NaHCO3 solution, brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by MPLC (silica gel; 0% to 20% ethyl acetate:hexane gradient) gave the title compound. HPLC/MS: 460.9 (M+1), 462.9 (M+3); Rt=4.35 min.

Workup

customThe reaction mixture was quenched at 0° C. with 10% aqueous NaHSO4 solution
customThe reaction mixture was partitioned between ethyl acetate and 10% NaHSO4 aqueous solution
washThe organic layer was washed twice with saturated NaHCO3 solution, brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by MPLC (silica gel; 0% to 20% ethyl acetate:hexane gradient)

Sources & evidence

ORD record: ord-18a54a893318434ebd0c2f0f966da44b
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07091216B2

Reaction notes

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