Diisopropylethylamine → N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-fluoro-4-trifluoromethyl-benzamide

HRID 448496ノート

反応式

HRID 448496 の反応式
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].[F:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[C:33]([F:36])([F:35])[F:34])[C:27](Cl)=[O:28].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:27](=[O:28])[C:26]3[CH:30]=[CH:31][C:32]([C:33]([F:34])([F:35])[F:36])=[C:24]([F:23])[CH:25]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 27347093-Fluoro-4-(trifluoromethyl)benzoyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

生成物 1

HCID 58307346N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-fluoro-4-trifluoromethyl-benzamide収率 57.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To the stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) and 3-fluoro-4-trifluoromethylbenzoyl chloride (0.6 g, 2.8 mmol) in dry methylene chloride (60 mL), was added diisopropylethylamine (0.7 g, 5.4 mmol). After stirring at room temperature overnight, the reaction mixture was quenched with methanol (1 mL) and washed with water (2×40 mL) and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH: CH2Cl2 3:97) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-fluoro-4-trifluoromethyl-benzamide (0.6 g, 53%) as a white solid: mp 165-167° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=8.20 min. (99%); 1H NMR (DMSO-d6) δ 2.06-2.12 (m, 1H), 2.53-2.65 (m, 2H), 2.87-2.93 (m, 1H), 4.98 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5.3 and 12.5 Hz, 1H), 7.76-7.84 (m, 3H), 7.95-8.01 (m, 3H), 9.45 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.97, 30.92, 38.54, 48.87, 115.88 (116.17), 118.56 (118.72, 119.00, 119.16), 122.30, 123.94 (123.98), 120.52 (124.13), 127.25, 127.74 (127.80), 131.55, 133.24, 134.83, 138.51, 140.42 (140.52), 157.04 (160.38), 164.19, 166.91, 167.48, 169.81, 172.74; Anal. Calcd. for C22H15N3O5F4: C, 55.35; H, 3.17; N, 8.80; F, 15.92. Found: C, 55.00; H, 2.95; N, 8.80; F, 15.92.

後処理

  1. customthe reaction mixture was quenched with methanol (1 mL)
  2. washwashed with water (2×40 mL) and brine (40 mL)
  3. dry with materialdried over MgSO4
  4. customSolvent was removed in vacuo
  5. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH: CH2Cl2 3:97)

出典と根拠

ORDレコード
ord-3ffe6b0abcc740609bfcd89101c86407
出典データセット
uspto-grants-2013_07
特許番号
US08481568B2

反応ノート

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