3-(Chloromethyl)benzo(b)thiophene → 2-(3-Benzo[b]thiophen-3-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

HRID 343212ノート

反応式

HRID 343212 の反応式
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:4](=[O:34])[CH2:3]1.Cl[CH2:36][C:37]1[C:38]2[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=2[S:40][CH:41]=1>CN(C=O)C.C1(C)C=CC=CC=1>[S:40]1[CH:41]=[C:37]([CH2:36][CH:3]2[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[O:11])[C:7]3[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:4]2=[O:34])[C:38]2[CH:45]=[CH:44][CH:43]=[CH:42][C:39]1=2

参加物

5

反応物 2

HCID 766803-(Chloromethyl)benzo(b)thiopheneHCID 107900232-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

生成物 1

HCID 106036912-(3-Benzo[b]thiophen-3-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide収率 55.7%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

To a stirring solution of 300 mg (0.66 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide, prepared as in Intermediate 4, in 15 mL DMF at 0° C. is added dropwise over 5 min 1.45 mL (0.72 mmol, 1.1 equiv) of a 0.5M solution of KN(TMS)2 in toluene. The resulting solution is stirred 10 min, and then a solution of 132 mg (0.72 mmol, 1.1 equiv) of 3-chloromethylbenzo[b]thiophene (Wolf, G.; Zymalkowski, F. Arch. Pharm. 1976, 279) in 1 mL DMF is added. The resulting solution is stirred 2 h at RT and then quenched with 5 mL of H2O. The reaction mixture is poured into 50 mL of Et2O and extracted with H2O (2×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification of the material by silica gel MPLC on an Si60 column using hexane/EtOAc 5/2 as eluent followed by lyophilization in acetonitrile/H2O afforded 222 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ7.79 (m, 2H), 7.44-6.93 (m, 15H), 6.88 (dd, 1H, J=1.5, 8.1), 5.03 (m, 1H), 4.42 (d, 1H, J=16.6), 4.09 (d, 1H, J=16.6), 3.85 (s, 3H), 3.80 (t, 1H, J=6.6), 3.61 (m, 2H), 1.10 (t, 6H, J=6.8); low resolution MS (FAB)m/e 604 (MH+), 439.

後処理

  1. stirringThe resulting solution is stirred 2 h at RT
  2. customquenched with 5 mL of H2O
  3. additionThe reaction mixture is poured into 50 mL of Et2O
  4. extractionextracted with H2O (2×50 mL)
  5. customThe organic layer is separated
  6. dry with materialdried (MgSO4)
  7. customthe solvents removed in vacuo
  8. customPurification of the material by silica gel MPLC on an Si60 column

出典と根拠

ORDレコード
ord-ca1353830c7a418396d7d206e15cf929
出典データセット
uspto-grants-1999_01
特許番号
US05859007

反応ノート

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