1,1'-Carbonyldiimidazole → N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methanesulfonyl-benzamide

HRID 331573

반응식

HRID 331573 반응식
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C1N=CN(C(N2C=NC=C2)=O)C=1.CS(O)(=O)=O.[NH2:31][CH2:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[C:38](=[O:42])[N:37]([CH:43]1[CH2:48][CH2:47][C:46](=[O:49])[NH:45][C:44]1=[O:50])[CH2:36]2>CN(C=O)C>[O:50]=[C:44]1[CH:43]([N:37]2[CH2:36][C:35]3[C:39](=[CH:40][CH:41]=[C:33]([CH2:32][NH:31][C:9](=[O:11])[C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:13][CH:12]=4)[CH:34]=3)[C:38]2=[O:42])[CH2:48][CH2:47][C:46](=[O:49])[NH:45]1

참가 물질

5

반응물 3

HCID 682631,1'-CarbonyldiimidazoleHCID 77670p-(Methylsulphonyl)benzoic acidHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

생성물 1

HCID 44538015N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methanesulfonyl-benzamide수율 71%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
40 °C

실험 절차

A mixture of 4-methylsulphonylbenzoic acid (0.28 g, 1.4 mmol) and CDI (0.24 g, 1.5 mmol) was stirred in DMF (30 mL) at 40° C. for 4 hours. 3-(5-Aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.50 g, 1.4 mmol) was added and the mixture was stirred at 40° C. for 2 h. The mixture was quenched with 4% aqueous HCl (30 mL) and the resulting precipitate was filtered, washed with water (30 mL) and dried in vacuo providing N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methanesulfonyl-benzamide as a white solid, (0.44 g, 71% yield); mp 260-262° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 50/50 CH3CN/0.1% H3PO4, 4.08 (98.31%); 1H NMR (DMSO-d6) δ 1.96-2.03 (m, 1H), 2.31-2.46 (m, 1H), 2.57-2.63 (m, 1H), 2.86-2.98 (m, 1H), 3.27 (s, 3H), 4.31 (d, 1H, J=17.4 Hz), 4.45 (d, 1H, J=17.4 Hz), 4.63 (d, 2H, J=5.7 Hz), 5.11 (dd, 1H, J=13.2 Hz, J=4.8 Hz), 7.48 (d, 1H, J=8.1 Hz), 7.56 (s, 1H), 7.71 (d, 1H, J=7.8 Hz), 8.05 (d, 2H, J=8.4 Hz), 8.14 (d, 2H, J=8.4 Hz), 9.42 (t, 1H, J=6.0 Hz), 10.99 (s, 1H). 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.9, 43.3, 47.1, 51.6, 122.1, 123.0, 127.1, 128.3, 130.4, 138.6, 142.4, 143.0, 143.5, 165.0, 167.9, 171.0, 172.8; LCMS: MH=456; Anal. Calcd for C22H21N3O6S: C, 58.01; H, 4.65; N, 9.23. Found: C, 58.15; H, 4.52; N, 9.04.

후처리

  1. customThe mixture was quenched with 4% aqueous HCl (30 mL)
  2. filtrationthe resulting precipitate was filtered
  3. washwashed with water (30 mL)
  4. customdried in vacuo

출처 및 근거

ORD 기록
ord-61931dff19b2450b9b1b9ba1071a0f99
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877780B2

연결된 노트

불러오는 중…