Triethylamine → thiazole-2-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide

HRID 448503ノート

反応式

HRID 448503 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].C(N(CC)CC)C.[S:30]1[CH:34]=[CH:33][N:32]=[C:31]1[C:35](Cl)=[O:36]>CC#N>[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:35]([C:31]3[S:30][CH:34]=[CH:33][N:32]=3)=[O:36])[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 8471TriethylamineHCID 27952111,3-Thiazole-2-carbonyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

生成物 1

HCID 58827320thiazole-2-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide収率 74.6%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.57 g, 1.75 mmol) in CH3CN (10 ml), were added triethyl amine (0.61 mL, 4.4 mmol) and 1,3-thiazole-2-carbonyl-chloride (1.07 g, 4.5 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The resulting oil was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2) to afford thiazole-2-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide as a white solid (0.52 g, 74%): mp, 189-191° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, gradient from 10/90 (CH3CN/H2O) to 95/5(CH3CN/H2O) in 10 minutes: tR=5.9 min (97%); 1H NMR (DMSO-d6): δ 2.05-2.12 (m, 1H), 2.53-2.65 (m, 2H), 2.86-2.98 (m, 1H), 4.94 (d, J=6.2 Hz, 2H), 5.18 (dd, J=5, 11 Hz, 1H), 7.68-8.10 (m, 5H), 9.50 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.96, 30.92, 38.32, 48.88, 121.98, 125.99, 127.17, 131.56, 132.92, 134.85, 138.43, 143.98, 159.59, 163.18, 166.93, 167.51, 169.81, 172.73. Anal Calcd for C18H14N4O5S: C, 54.27; H, 3.54; N, 14.06; S, 8.05. Found: C, 53.98; H, 3.49; N, 13.75; S, 8.22.

後処理

  1. customa suspension was obtained
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe resulting oil was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-59dba3eddcfa4a5b8d17c0018de5c50d
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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