3-Bromopyridine → 1H-Indole-2-carboxylic acid {1[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide

HRID 1599068ノート

反応式

HRID 1599068 の反応式
[CH:1]([C:4]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)([C:30](=[O:32])[NH2:31])[N:5]1[C:11](=[O:12])[CH:10]([NH:13][C:14]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[C:9](=[O:25])[NH:8][C:7]2[CH:26]=[CH:27][CH:28]=[CH:29][C:6]1=2)([CH3:3])[CH3:2].Br[C:42]1[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=1.[K+].C([O-])(=O)C>CN(C=O)C.[Cu]>[CH:1]([C:4]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)([C:30](=[O:32])[NH2:31])[N:5]1[C:11](=[O:12])[CH:10]([NH:13][C:14]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[C:9](=[O:25])[N:8]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)[C:7]2[CH:26]=[CH:27][CH:28]=[CH:29][C:6]1=2)([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 122863-BromopyridineHCID 517044Potassium AcetateHCID 867524091H-Indole-2-carboxylic acid {1-[isopropyl-(4-methoxyphenyl)-carbamoylmethyl]-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide

生成物 1

HCID 867524081H-Indole-2-carboxylic acid {1[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide収率 11.9%

試薬・触媒・溶媒 2

HCID 23978Copper触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

To a solution of 1H-Indole-2-carboxylic acid {1[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-2,3,4,5-tetrhydro-1H-benzo[b][1,4]diazepine-3-yl}amide (0.14 g, 0.26 mmol) and 3-bromopyridine (40 μL, 0.42 mmol)in DMF (1 mL) was added copper powder (46 mg, 0.73 mmol) and acetic acid potassium salt (38 mg, 0.73 mmol). The heterogenous solution was stirred at 100° C. for 15 h and subsequently hot filtered through celite and washed with methanol. The resulting precipitate was filtered and purified by RPHPLC (40-60% C. over 30 min) to yield the title compound (19 mg) as a white lyophile: Tr=8.7 min (40-60% C. over 30 min); 1HNMR (d6 -Acetone, 300 MHz) δ 10.98 (s, 1H), 9.02 (s, 1H), 8.76 (s, 1H), 7.85 (d, 1H, J=8.8), 7.5 (m, 15H), 5.68 (d, 1H, J=7.6), 5.02 (m, 1H), 4.65 (ABq, 2H, J=16.8, 135), 4.02 (s, 3H), 2.19 (d, 3H, J=2.0), 2.18 (d, 3H, J=2.0); low resolution MS(FAB) m/e 617 (MH+).

後処理

  1. filtrationsubsequently hot filtered through celite
  2. washwashed with methanol
  3. filtrationThe resulting precipitate was filtered
  4. custompurified by RPHPLC (40-60% C. over 30 min)

出典と根拠

ORDレコード
ord-d8ba41b7ccc740acab4fffe5d3714b4a
出典データセット
uspto-grants-1998_04
特許番号
US05739129

反応ノート

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