Trifluoroacetic acid → 3-Amino-N-(2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl)azetidine-1-sulfonamide
Reaction equation
[F:1][C:2]1[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:3]=1[CH2:4][S:5][C:6]1[N:11]=[C:10]([NH:12][S:13]([N:16]2[CH2:19][CH:18]([NH:20]C(=O)OC(C)(C)C)[CH2:17]2)(=[O:15])=[O:14])[CH:9]=[C:8]([O:28][CH3:29])[N:7]=1.C(O)(C(F)(F)F)=O>CO>[NH2:20][CH:18]1[CH2:19][N:16]([S:13]([NH:12][C:10]2[CH:9]=[C:8]([O:28][CH3:29])[N:7]=[C:6]([S:5][CH2:4][C:3]3[CH:30]=[CH:31][CH:32]=[C:33]([F:34])[C:2]=3[F:1])[N:11]=2)(=[O:14])=[O:15])[CH2:17]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of tert-butyl {1-[({2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}amino)sulfonyl]azetidin-3-yl}carbamate (the product of step ii, 0.48 g) and TFA (2 ml) in methanol (6 ml) was stirred at room temperature for 1.5 h then the volatiles evaporated and 7M ammonia in methanol (6 ml) added to the residue. The solution was stirred for 2 h then the volatiles evaporated and the residue purified by column chromatography on silica using a 2-8% mixture of methanol in DCM and then further purified by reverse phase HPLC (gradient 5-95% acetonitrile in 0.1% aqueous ammonium acetate) to afford the title compound as a white solid. Yield: 73 mg
Workup
- customthe volatiles evaporated
- addition7M ammonia in methanol (6 ml) added to the residue
- customthe volatiles evaporated
- customthe residue purified by column chromatography on silica using a 2-8% mixture of methanol in DCM
- customfurther purified by reverse phase HPLC (gradient 5-95% acetonitrile in 0.1% aqueous ammonium acetate)
Sources & evidence
- ORD record
- ord-f982daab8922440ca18e74029fd1e54a
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08722883B2
Reaction notes
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