Cyclohexyl isocyanate → 1-Cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-YL)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea

HRID 448277

反応式

HRID 448277 の反応式
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[CH:33]1([N:39]=[C:40]=[O:41])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>C(#N)C>[CH:33]1([NH:39][C:40]([NH:13][CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH2:17][N:18]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:19]3=[O:24])=[O:41])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

参加物

5

反応物 3

HCID 18502Cyclohexyl isocyanateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

生成物 1

HCID 161169551-Cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-YL)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea収率 16%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.4 g, 2.9 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.6 g, 1.9 mmol) in acetonitrile (100 mL). The mixture was heated for 30 minutes, then cooled to room temperature. Cyclohexyl isocyanate (0.4 g, 2.9 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was filtered and the solid was stirred with water (25 mL) to give 0.9 g of crude product. The crude product was recrystallized from methanol to give 1-cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.12 g, 16%) as a white solid: mp 309-311° C.; 1H NMR (DMSO-d6) δ 0.97-1.75 (m, 10H), 1.99-2.04 (m, 1H), 2.32-2.64 (m, 3H), 2.86-2.98 (m, 1H), 4.27-4.51 (m, 4H), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 5.86 (d, J=7.9 Hz, 1H), 6.26 (t, J=5.5 Hz, 1H, NH), 7.47-7.62 (m, 3H, Ar), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.64, 24.44, 25.29, 31.16, 33.32, 46.09, 47.50, 47.85, 51.47, 121.36, 128.18, 130.26, 131.61, 136.28, 139.77, 157.20, 168.09, 170.97, 172.82; Anal. calcd. for C21H26N4O4: C, 63.30; H, 6.58; N, 14.06. Found: C, 63.18; N, 6.58; N, 13.99.

後処理

  1. temperatureThe mixture was heated for 30 minutes
  2. filtrationThe mixture was filtered
  3. stirringthe solid was stirred with water (25 mL)
  4. customto give 0.9 g of crude product
  5. customThe crude product was recrystallized from methanol

出典と根拠

ORDレコード
ord-7d078c0149cb4941b58fba04b2384487
出典データセット
uspto-grants-2013_07
特許番号
US08481568B2

関連ノート

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