Ethyl Acetate → N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methylsulfanyl-benzamide

HRID 63447

반응식

HRID 63447 반응식
[CH3:1][S:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:25][CH2:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[N:31]([C:37]1([CH3:45])[CH2:42][CH2:41][C:40](=[O:43])[NH:39][C:38]1=[O:44])[C:30]2=[O:46].CCOC(C)=O>CN(C)C=O>[CH3:45][C:37]1([N:31]2[C:30](=[O:46])[C:29]3[C:33](=[CH:34][CH:35]=[C:27]([CH2:26][NH:25][C:7](=[O:9])[C:6]4[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:11][CH:10]=4)[CH:28]=3)[C:32]2=[O:36])[CH2:42][CH2:41][C:40](=[O:43])[NH:39][C:38]1=[O:44]

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 832304-(Methylthio)benzoic acidHCID 670232045-Aminomethyl-2-(3-methyl-2,6-dioxo-piperidin-3-yl)isoindole-1,3-dione hydrochloride

생성물 1

HCID 67023358N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methylsulfanyl-benzamide수율 26.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
40 °C

실험 절차

A stirred mixture of 4-(methylthio)benzoic acid (0.34 g, 2.00 mmol) and CDI (0.34 g, 2.10 mmol) in N,N-dimethylformamide (20 mL) was heated to 40° C. under nitrogen. After 2 h, 5-aminomethyl-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.68 g, 2.00 mmol) was added and the mixture was heated at 40° C. for 2 h. The mixture was cooled to rt and EtOAc (75 mL) was added. The organic layer was washed with sat. aq. NaHCO3 (3×100 mL) then concentrated in vacuo. The crude residue was purified by column chromatography (CH2Cl2MeOH, gradient, product eluted after 4.7 min). The product fractions were combined and concentrated to give N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methylsulfanyl-benzamide as a white solid (0.24 g, 26% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 4.74 min (98.27%); mp: 218-220° C.; 1H NMR (DMSO-d6) δ 1.88 (s, 3H), 1.99-2.10 (m, 1H), 2.51-2.61 (m, 5H), 2.62-2.78 (m, 1H), 4.61 (d, J=5.9 Hz, 2H), 7.34 (d, J=8.3 Hz, 2H), 7.64-7.96 (m, 5H), 9.17 (t, J=5.9 Hz, 1H), 11.01 (s, 1H); 13C NMR (DMSO-d6) δ 14.12, 21.02, 28.57, 29.09, 42.57, 58.76, 121.60, 123.19, 124.95, 127.74, 129.59, 129.93, 131.38, 133.38, 142.84, 147.52, 165.86, 167.73, 167.88, 172.13, 172.19; LCMS: MH=452; Anal Calcd for C23H21N3O5S: C, 61.18; H, 4.69; N, 9.31. Found: C, 60.82; H, 4.85; N, 8.96.

후처리

  1. temperaturethe mixture was heated at 40° C. for 2 h
  2. temperatureThe mixture was cooled to rt
  3. washThe organic layer was washed with sat. aq. NaHCO3 (3×100 mL)
  4. concentrationthen concentrated in vacuo
  5. customThe crude residue was purified by column chromatography (CH2Cl2MeOH, gradient, product eluted after 4.7 min)
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-53903d916f824f7b94437c8f58753368
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447070B2

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