Hydrochloric Acid → 1-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-urea

HRID 331660

반응식

HRID 331660 반응식
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH:13]1[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]1=[O:20])[CH2:6]2.[N:21]([C:24]1[CH:33]=[CH:32][C:27]2[O:28][CH2:29][CH2:30][O:31][C:26]=2[CH:25]=1)=[C:22]=[O:23].C(N(CC)CC)C.Cl>C(#N)C>[O:28]1[C:27]2[CH:32]=[CH:33][C:24]([NH:21][C:22]([NH:1][CH2:2][C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][CH:11]=3)[C:8](=[O:12])[N:7]([CH:13]3[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]3=[O:20])[CH2:6]4)=[O:23])=[CH:25][C:26]=2[O:31][CH2:30][CH2:29]1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27761726-Isocyanato-2,3-dihydro-1,4-benzodioxineHCID 594432803-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione

생성물 1

HCID 445390191-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-urea수율 91%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (0.37 g, 1.00 mmol) and 6-isocyanato-2,3-dihydro-benzo[1,4]dioxine (0.18 g, 1.00 mmol) in acetonitrile (10 mL), was added triethylamine (0.28 mL, 2.00 mmol) at room temperature under nitrogen. After 2 h, dil. aq. HCl (25 mL) was added. The solids were collected by filtration and washed with water (3×30 mL). The product was slurried in EtOAc for 24 h, then filtered and dried in vacuo to give 1-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (0.41 g, 91% yield): HPLC: Waters Nova-Pak C18 column, 3.9×150 mm, 4 μm; 10/90 to 90/10 CH3CN/0.1% aq H3PO4, Gradient over 15 min, 1.0 mL/min, 7.26 min (99.20%); mp: 230-232° C.; 1H NMR (DMSO-d6) δ 1.86-2.10 (m, 1H, CHH), 2.27-2.47 (m, 1H, CHH), 2.59 (d, J=17.6 Hz, 1H, CHH), 2.79-3.04 (m, 1H, CHH), 4.17 (q, J=4.8 Hz, 4H, CH2, CH2), 4.30 (d, J=17.4 Hz, 1H, CHH), 4.36-4.53 (m, 3H, CHH, CH2), 5.11 (dd, J=5.1, 13.2 Hz, 1H, CH), 6.62 (t, J=5.9 Hz, 1H, NH), 6.66-6.83 (m, 2H, Ar), 7.05 (d, J=2.1 Hz, 1H, Ar), 7.43 (d, J=7.7 Hz, 1H, Ar), 7.50 (s, 1H, Ar), 7.69 (d, J=7.7 Hz, 1H, Ar), 8.41 (s, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.49, 31.18, 42.76, 47.10, 51.56, 63.81, 64.19, 107.05, 111.15, 116.66, 121.85, 122.91, 126.86, 130.26, 134.08, 137.90, 142.36, 142.99, 144.94, 155.28, 167.95, 170.99, 172.85; LCMS: MH=451; Anal Calcd for C23H22N4O6: C, 61.33; H, 4.92; N, 12.44. Found: C, 61.14; H, 4.82; N, 12.40.

후처리

  1. filtrationThe solids were collected by filtration
  2. washwashed with water (3×30 mL)
  3. waitThe product was slurried in EtOAc for 24 h
  4. filtrationfiltered
  5. customdried in vacuo

출처 및 근거

ORD 기록
ord-cb1b68cc45bb4bf6b1b91f2902ec0ba6
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877780B2

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