3-Bromopyridine → 2-(7-Fluoro-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 1599097ノート

反応式

HRID 1599097 の反応式
[F:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:13][C:14]([N:16]([CH:25]([CH3:27])[CH3:26])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[O:15])[C:7](=[O:12])[CH2:8][C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1.C([O-])(=O)C.[K+].Br[C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1>CN(C)C=O.[Cu]>[F:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:13][C:14]([N:16]([CH:25]([CH3:27])[CH3:26])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[O:15])[C:7](=[O:12])[CH2:8][C:9](=[O:11])[N:10]([C:36]3[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=3)[C:4]=2[CH:3]=1

参加物

6

反応物 3

HCID 122863-Bromopyridine2 回HCID 517044Potassium AcetateHCID 540958782-(7-Fluoro-2,4-dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

生成物 1

HCID 540873952-(7-Fluoro-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide収率 67.3%

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

A mixture of 0.880 g of 2-(7-Fluoro-2,4-dioxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (2.20 mmol), 420 mg of copper (bronze, 6.61 mmol, 3 equiv), 476 mg of potassium acetate (4.85 mmol, 2.2 equiv), and 0.290 mL of 3-bromopyridine (4.85 mmol, 2.2 equiv) in 10 mL of dimethylformamide was heated at 100° C. under nitrogen for 3 hrs. An additional 0.132 mL of 3-bromopyridine (2.43 mmol, 1.1 equiv) was added and the reaction was maintained for an additional 2 hrs. The reaction mixture was cooled to ambient temperature, filtered through a sintered glass funnel and then evaporated in vacuo to a residue. The residue was partitioned between ethyl acetate and aqueous ammonium hydroxide (5 mL conc. diluted to 100 mL). After separating the layers, the organic layer was washed with aqueous ammonium hydroxide (5 mL conc. diluted to 100 mL), and then saturated aqueous brine. The organic phase was then extracted three times with aqueous HCl (1N). The acid layers were combined and neutralized with aqueous sodium hydroxide (1N). The neutralized mixture was extracted twice with methylene chloride. The methylene chloride layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to a residue. The residue was triturated with hexane and then concentrated in vacuo to provide 0.705 g of the title compound as a tan solid. H NMR (300 MHz, CDCl3) d 8.60 (m, 2H), 8.08 (b, 1H), 7.54 (b, 1H), 7.39 (m, 1H), 7.15 (m, 2H), 7.00 (m, 3H), 6.57 (dd, 1H, J=2.7, 9.2), 4.95 (m, 1H), 4.32 (d, 1H, J=17.9), 4.14 (d, 1H, J=17.8), 3.85 (s, 3H), 3.61 (d, 1H, J=12.1), 3.52 (d, 1H, J=12.1), 1.06 (d, 6H, J=6.8); low resolution MS (FAB)m/e 477 (MH+).

後処理

  1. temperaturethe reaction was maintained for an additional 2 hrs
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationfiltered through a sintered glass funnel
  4. customevaporated in vacuo to a residue
  5. customThe residue was partitioned between ethyl acetate and aqueous ammonium hydroxide (5 mL conc. diluted to 100 mL)
  6. customAfter separating the layers
  7. washthe organic layer was washed with aqueous ammonium hydroxide (5 mL conc. diluted to 100 mL)
  8. extractionThe organic phase was then extracted three times with aqueous HCl (1N)
  9. extractionThe neutralized mixture was extracted twice with methylene chloride
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo to a residue
  13. customThe residue was triturated with hexane
  14. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-e4966b9511754bc0a64cc6785a0becc5
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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