Water → 2-((4,6-difluoro-1H-indol-3-yl)sulfonyl)-N-(5-methylisoxazol-3-yl)acetamide
Reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4](SCC(O)=O)=[CH:5][NH:6]2.[NH2:17][C:18]1[CH:22]=[C:21]([CH3:23])[O:20][N:19]=1.C1CN(C(Cl)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl[CH:53](Cl)[CH3:54].O[O:57][S:58]([O-:60])=O.[K+].[OH2:62]>CO>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([S:58]([CH2:53][C:54]([NH:17][C:18]1[CH:22]=[C:21]([CH3:23])[O:20][N:19]=1)=[O:62])(=[O:60])=[O:57])=[CH:5][NH:6]2Participants
Reactant 7
Product 1
Reagents, catalysts & solvents 1
Procedure
2-((4,6-difluoro-1H-indol-3-yl)thio)acetic acid (160 mg, 0.66 mmol) from Step B, 3-amino-5-methyl-isoxazole (130 mg, 1.32 mmol), PyClu (440 mg, 1.32 mmol), and DIEA (289 μL, 1.65 mmol) were added to dichloroethane (5 mL) and microwave irradiated at 110° C. for 30 minutes. The solvent was removed in vacuo and the remaining residue was dissolved in 5 mL (9:1, methanol:water) and oxone (641 mg, 1.0 mmol) was added and this mixture was stirred at ambient temperature overnight. Water (5 mL) was added and the mixture extracted with ethyl acetate (3×3 mL). The organics were combined, dried over magnesium sulfate, and concentrated in vacuo to give an oily residue which was purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min) to yield the desired product (62.0 mg, 0.174 mmol, 26% yield over 2 steps). LCMS>99% at 220 nm, RT=1.15 min, m/z=356 (M+1).
Workup
- customirradiated at 110° C. for 30 minutes
- customThe solvent was removed in vacuo
- additionwas added
- extractionthe mixture extracted with ethyl acetate (3×3 mL)
- dry with materialdried over magnesium sulfate
- concentrationconcentrated in vacuo
- customto give an oily residue which
- customwas purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min)
Sources & evidence
- ORD record
- ord-115b1c33249e4ed2b3fdc188196fe7f4
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772509B2
Reaction notes
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