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

HRID 448498ノート

反応式

HRID 448498 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[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27].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:26](=[O:27])[C:25]3[CH:29]=[CH:30][CH:31]=[C:32]([C:33]([F:34])([F:35])[F:36])[C:24]=3[F:23])[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 27375592-Fluoro-3-(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 67228871N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-fluoro-3-trifluoromethyl-benzamide収率 76.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) and 2-fluoro-3-trifluoromethyl-benzoyl chloride (0.6 g, 2.8 mmol) in dry methylene chloride (60 mL), was added diisopropylethylamine (0.7 g, 5.4 mmol). The mixture was stirred at room temperature overnight then quenched with methanol (1 mL). The resulting suspension was filtered and the solid was washed with methylene chloride to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-fluoro-3-trifluoromethyl-benzamide (0.8 g, 72%) as a white solid: mp 155-157° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.23 min. (99%); 1H NMR (DMSO-d6) δ 2.04-2.11 (s, 1H), 2.53-2.64 (m, 2H), 2.85-2.97 (m, 1H), 4.96 (d, J=5.8 Hz, 2H), 5.15-5.21 (dd, J=5.3 and 12.6 Hz, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.79-8.01 (m, 5H), 9.26 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.96, 30.91, 38.46, 48.87, 117.03 (117.29, 117.45), 120.65 (124.26), 122.03, 125.09 (125.15), 125.45 (125.64), 127.22, 129.24 (129.29), 131.58, 132.97, 134.89, 138.41, 154.37 (157.77), 162.90, 166.91, 167.45, 169.80, 172.73; Anal. Calcd. for C22H15N3O5F4: C, 55.35; H, 3.17; N, 8.80; F, 15.92. Found: C, 55.13; H, 2.95; N, 8.73; F, 15.69.

後処理

  1. customthen quenched with methanol (1 mL)
  2. filtrationThe resulting suspension was filtered
  3. washthe solid was washed with methylene chloride

出典と根拠

ORDレコード
ord-1fd61717655443e8b042a6f2573a2b21
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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