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Methyl iodide → 2-(3-Benzo[b]thiophen-3-ylmethyl-3-methyl-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 343214
ノート
印刷プレビュー

反応式

HRID 343214 の反応式
[S:1]1[CH:5]=[C:4]([CH2:6][CH:7]2[C:13](=[O:14])[N:12]([CH2:15][C:16]([N:18]([CH:27]([CH3:29])[CH3:28])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:17])[C:11]3[CH:30]=[CH:31][CH:32]=[CH:33][C:10]=3[N:9]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:8]2=[O:40])[C:3]2[CH:41]=[CH:42][CH:43]=[CH:44][C:2]1=2.[CH3:45][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI>CN(C=O)C.C1COCC1>[S:1]1[CH:5]=[C:4]([CH2:6][C:7]2([CH3:45])[C:13](=[O:14])[N:12]([CH2:15][C:16]([N:18]([CH:27]([CH3:29])[CH3:28])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:17])[C:11]3[CH:30]=[CH:31][CH:32]=[CH:33][C:10]=3[N:9]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:8]2=[O:40])[C:3]2[CH:41]=[CH:42][CH:43]=[CH:44][C:2]1=2
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 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

生成物 1

HCID 676967932-(3-Benzo[b]thiophen-3-ylmethyl-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒
HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a stirring solution of 130 mg (0.22 mmol) of 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, prepared as in Example 37, in 5 mL of DMF at 0° C. is added 0.43 mL (0.43 mmol, 2.0 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and 27 μL (0.43 mmol, 2.0 equiv) of methyl iodide is added. The resulting solution is stirred 4 h at RT, warmed to 50° C. for 16 h, 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 3/1 as eluent followed by lyophilization in acetonitrile/H2O afforded 106 mg of the title compound as a white amorphous solid: 1H NMR (DMSO-d6, 300 MHz) δ7.92 (m, 1H), 7.66-7.05 (m, 16H), 6.81 (d, 1H, J=8.1), 4.85 (m, 1H), 4.31 (s, br, 2H), 3.80 (s, 3H), 2.97 (d, 1H, J=15.2), 2.77 (d, 1H, J=15.2), 1.20 (s, 3H), 1.00 (m, 6H); low resolution MS (FAB)m/e 618 (MH+), 617 (M+), 453; Anal. (C37H35N3O4S) Calcd. C, 71.71; H, 5.74; N, 6.76; S, 5.26 Found C, 71.94; H, 5.71; N, 6.80; S, 5.19.

後処理

  1. stirringThe resulting solution is stirred 4 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-c12eb515082745f6984a8cd969c61236
出典データセット
uspto-grants-1999_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05859007

反応ノート

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