Hydrochloric Acid → 1-(4-chloro-3-trifluoromethyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea

HRID 63499

반응식

HRID 63499 반응식
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]=[C:34]=[O:35])=[CH:29][C:28]=1[C:36]([F:39])([F:38])[F:37].Cl>CN(C=O)C>[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)=[O:35])=[CH:29][C:28]=1[C:36]([F:37])([F:38])[F:39]

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

생성물 1

HCID 445388311-(4-chloro-3-trifluoromethyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea수율 86%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

TEA (0.28 g, 2.8 mmol) was added to a mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.5 g, 1.4 mmol) and 4-chloro-3-(trifluoromethyl)phenyl isocyanate (0.31 g, 1.4 mmol) in DMF (30 mL) at 0° C. The mixture stirred at 0° C. for 3 h, and then 4% aqueous HCl (30 mL) was added. The solid precipitate was filtered and dried in vacuo providing 1-(4-chloro-3-trifluoromethyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid, (0.57 g, 86% yield); mp 261-263° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 8.57 (98.52%); 1H NMR (DMSO-d6) δ 1.98-2.02 (m, 1H), 2.13-2.46 (m, 1H), 2.58-2.63 (m, 1H), 2.86-2.98 (m, 1H), 4.28-4.48 (m, 4H), 5.11 (dd, 1H, J=13.2 Hz, J=5.1 Hz), 6.98 (t, 1H, J=6.0 Hz), 7.45 (d, 1H, J=8.1 Hz), 7.54 (d, 2H, J=11.7 Hz), 7.61 (dd, 1H, J=8.7 Hz, J=2.1 Hz), 7.70 (d, 1H, J=7.8 Hz), 8.09 (d, 1H, J=2.4 Hz), 9.18 (s, 1H), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.8, 47.1, 51.6, 116.2 (q, J=5.6 Hz), 121.5, 121.9, 122.4, 122.8 (q, J=271 Hz), 122.9, 126.6 (q, J=30 Hz), 126.9, 130.3, 131.8, 140.0, 142.4, 144.5, 154.9, 167.9, 171.0, 172.8; LCMS: MH=495, 497; Anal. Calcd for C22H18ClF3N4O4+0.1H2O: C, 53.20; H, 3.69; N, 11.28. Found: C, 52.83; H, 3.47; N, 11.15.

후처리

  1. filtrationThe solid precipitate was filtered
  2. customdried in vacuo

출처 및 근거

ORD 기록
ord-8338b937a20b4b61a502da07da4b469e
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447070B2

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