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

HRID 63484

反応式

HRID 63484 の反応式
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[CH2:7]2.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[N:30]=[C:31]=[O:32].C(N(CC)CC)C.Cl>C(#N)C>[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[NH:30][C:31]([NH:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[CH2:7]2)=[O:32]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 6045371,3-Dichloro-2-isocyanatobenzeneHCID 665895253-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride

生成物 1

HCID 445387281-(2,6-dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea収率 29.4%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred mixture of 3-(5-Aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.423 g, 1.15 mmol) and 2,6-dichlorophenyl isocyanate (0.216 g, 1.15 mmol) in acetonitrile (10 mL), was added triethylamine (0.32 mL, 2.30 mmol) at room temperature under nitrogen. After 1 h, 1N aq. HCl (10 mL) was added and the mixture was stirred for 10 min. The product was isolated by filtration, washed with 1N aq. HCl (20 mL), acetonitrile (20 mL) and dried overnight in vacuo to give 1-(2,6-dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (0.156 g, 29% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.74 min (99.7%); mp: 238-240° C.; 1H NMR (DMSO-d6) δ 1.93-2.08 (m, 1H, CH), 2.31-2.47 (m, 1H, CH), 2.60 (d, J=17.0 Hz, 1H, CH), 2.84-3.01 (m, 1H, CH), 4.24-4.51 (m, 4H, CH2, CH2), 5.11 (dd, J=5.0, 13.3 Hz, 1H, NCH), 6.96 (t, J=5.9 Hz, 1H, NH), 7.23-7.33 (m, 1H, Ar), 7.42-7.57 (m, 4H, Ar), 7.69 (d, J=7.7 Hz, 1H, Ar), 8.19 (s, 1H, NH), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.48, 31.20, 43.02, 47.07, 51.56, 121.66, 122.85, 126.73, 128.12, 128.38, 130.23, 133.88, 134.07, 142.30, 144.96, 155.13, 167.96, 171.01, 172.86; LCMS: MH=461, 463; Anal Calcd for C21H18N4O4Cl2+0.1H2O: C, 54.47; H, 3.96; N, 12.10; Cl, 15.31. Found: C, 54.12; H, 3.71; N, 11.85; Cl, 15.31.

後処理

  1. customThe product was isolated by filtration
  2. washwashed with 1N aq. HCl (20 mL), acetonitrile (20 mL)
  3. customdried overnight in vacuo

出典と根拠

ORDレコード
ord-d8abe00f76d94add808bc484493d5466
出典データセット
uspto-grants-2016_09
特許番号
US09447070B2

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