Bis(2-chloroethyl) ether → (2,4-Bis-benzyloxy-5-isopropyl-phenyl)-(5-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-methanone

HRID 41426

反応式

HRID 41426 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([C:13]1[CH:18]=[C:17]([CH:19]([CH3:21])[CH3:20])[C:16]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:15][C:14]=1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:12])[CH2:5]2.Cl[CH2:39][CH2:40][O:41][CH2:42][CH2:43]Cl.CCN(C(C)C)C(C)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)CCC1>[CH2:31]([O:30][C:14]1[CH:15]=[C:16]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:17]([CH:19]([CH3:21])[CH3:20])=[CH:18][C:13]=1[C:11]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([N:1]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH:3]=2)[CH2:7]1)=[O:12])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

参加物

6

反応物 3

HCID 8115Bis(2-chloroethyl) ether2 回HCID 81531Diisopropylethylamine2 回HCID 66672407(5-Amino-1,3-dihydro-isoindol-2-yl)-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-methanone

生成物 1

HCID 59263147(2,4-Bis-benzyloxy-5-isopropyl-phenyl)-(5-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-methanone

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
150 °C

実験手順

A mixture of (5-amino-1,3-dihydro-isoindol-2-yl)-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-methanone (100 mg; 0.2 mmol), bis(2-chloroethyl)ether (30 μl; 1.1 equiv.), Hunigs base (125 μl; 3.5 equiv.) and tetrabutylammonium iodide (10 mg) in NMP (1 ml) was heated in a CEM microwave synthesiser at 150° C. for 30 minutes. A further 30 μA of Hunigs base and 125 μl of bis(2-chloroethyl)ether were added and heating repeated for the same time. The reaction mixture was partitioned between EtOAc and saturated NH4Cl solution, the EtOAc layer was separated, washed with more saturated NH4Cl solution, then brine, dried (MgSO4) and evaporated. Purification by flash column chromatography (1:2 then 1:1 then 2:1 EtOAc/P.E. as eluant) gave 60 mg of (2,4-bis-benzyloxy-5-isopropyl-phenyl)-(5-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-methanone. MS: [M−H]+ 563.

後処理

  1. temperatureheating
  2. customThe reaction mixture was partitioned between EtOAc and saturated NH4Cl solution
  3. customthe EtOAc layer was separated
  4. washwashed with more saturated NH4Cl solution
  5. dry with materialbrine, dried (MgSO4)
  6. customevaporated
  7. customPurification by flash column chromatography (1:2

出典と根拠

ORDレコード
ord-f463cbdc44ce466b9ba81c1394b8e8d7
出典データセット
uspto-grants-2013_09
特許番号
US08530469B2

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