Tetrahydrofuran → 3-Amino-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)furo[2,3-b]-pyridine-2-carbonitrile
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])=[N:10][C:11]([O:16][CH2:17][C:18]#[N:19])=[C:12]([CH:15]=2)[C:13]#[N:14])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>>[NH2:14][C:13]1[C:12]2[C:11](=[N:10][C:9]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH:15]=2)[O:16][C:17]=1[C:18]#[N:19]Participants
4
Conditions
- Temperature
- 0 °C
Procedure
A solution of the product from Step A (0.132 g; 0.319 mmol) in TB (3 mL) cooled to 0° C. was treated with 1 M solution of lithium bis(trimethylsilyl)amide in THF (701 μL; 0.701 mmol) and stirred at 0° C. under nitrogen for 15 minutes. The reaction mixture was warmed to room temperature and then stirred for an additional 15 minutes. The reaction mixture was partitioned between EtOAc 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 30% ethyl acetate-hexane gradient) gave the title compound. HPLC/MS: 413.9 (M+1), 415.9 (M+3); Rt=4.50 min.
Workup
- temperatureThe reaction mixture was warmed to room temperature
- stirringstirred for an additional 15 minutes
- customThe reaction mixture was partitioned between EtOAc 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 30% ethyl acetate-hexane gradient)
Sources & evidence
- ORD record
- ord-b22fb182a5a04572853f4b28447fe852
- Source dataset
- uspto-grants-2006_08
- Patent number
- US07091216B2
Reaction notes
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