Tetrahydrofuran → N-(2-acetamidophenyl)-3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:26])[C:10]1[C:15]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[CH:14][N:13]=[CH:12][C:11]=1[F:25].C[Si](C)(C)N[Si](C)(C)C.[O:36]1CC[CH2:38][CH2:37]1>>[C:37]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:26])[C:10]1[C:15]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[CH:14][N:13]=[CH:12][C:11]=1[F:25])(=[O:36])[CH3:38]Participants
4
Procedure
69 mg of N-(2-aminophenyl)-3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide (0.148 mmol, 1 eq.) were dissolved in 1 mL of terahydrofurane under a nitrogen athmoshere, then 0.592 ml of a hexamethyl disilazane solution (1M in THF, 4 eq.) were added and stirring was continued at room temperature for 18 h. The reaction mixture was partitioned between 20 ml of ethyl acetate and 15 ml of aqueouse HCL solution (1M). The aqueouse layer was reextracted twice with 20 ml of ethyl acetate each. The combined organic layers were washed with 20 ml of brine, dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to yield 14 mg (0.03 mmol, 19%) of the analytically pure target compound.
Workup
- customThe reaction mixture was partitioned between 20 ml of ethyl acetate and 15 ml of aqueouse HCL solution (1M)
- washThe combined organic layers were washed with 20 ml of brine
- dry with materialdried over a silicone
- filtrationfilter
- concentrationconcentrated in vacuo
- customThe residue was purified by flash chromatography
- customto yield 14 mg (0.03 mmol, 19%) of the analytically pure target compound
Sources & evidence
- ORD record
- ord-a820773abae44027a9b478bf8396776a
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09045429B2
Reaction notes
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