Trifluoroacetic acid → 5-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}-isothiazol-3(2H)-one 1,1-dioxide trifluoroacetate

反応式

[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([C:15]1([OH:39])[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[S:26][C:25]([C:27]3[S:31](=[O:33])(=[O:32])[N:30](C(C)(C)C)[C:29](=[O:38])[CH:28]=3)=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(O)(C(F)(F)F)=O.C([SiH](C(C)C)C(C)C)(C)C>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([C:15]1([OH:39])[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[S:26][C:25]([C:27]3[S:31](=[O:32])(=[O:33])[NH:30][C:29](=[O:38])[CH:28]=3)=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

参加物

反応物 3

HCID 6422Trifluoroacetic acid

HCID 138754Silane, tris(1-methylethyl)-

HCID 695978815-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}2-tertbutylisothiazol-3(2H)-one 1,1-dioxide trifluoroacetate

生成物 1

HCID 218795115-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}-isothiazol-3(2H)-one 1,1-dioxide trifluoroacetate収率 61%

実験手順

To 4.12-B in a microwave vial was added TFA (1.9 mL) and triisopropylsilane (0.06 mL). The reaction was microwave irradiated at 130° C. for 15 min. The solvents were evaporated and crude purified by reverse phase HPLC to afford 4.12-C (11 mg, 61%). 1H NMR (500 MHz, DMSO-d6): δ 9.24 (br s, 1H), 7.52 (d, J=8 Hz, 1H), 7.31 (d, J=8 Hz, 1H), 7.23 (m, 2H), 7.17 (m, 1H), 7.14 (m, 2H), 6.67 (s, 1H), 4.80 (br s, 1H), 4.55 (d, J=7 Hz, 2H), 3.18 (m, 2H), 3.08 (m, 2H), 2.67 (s, 2H), 1.63 (m, 2H), 1.56 (m, 2H); LCMS found for C20H22N2O4S2 (M+H)+: m/z=419.