Cyclopropanecarbohydrazide → Methyl 10-bromo-3-(2-(cyclopropanecarbonyl)hydrazinecarbonyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate

HRID 575423ノート

反応式

HRID 575423 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[C:13](I)=[C:14]([C:16]([O:18][CH3:19])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:21]=1.[CH:22]1([C:25]([NH:27][NH2:28])=[O:26])[CH2:24][CH2:23]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:50][C:32]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C)C=O.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[C:13]([C:32]([NH:28][NH:27][C:25]([CH:22]4[CH2:24][CH2:23]4)=[O:26])=[O:50])=[C:14]([C:16]([O:18][CH3:19])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:21]=1

参加物

7

反応物 3

HCID 81396CyclopropanecarbohydrazideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86693477Methyl 10-bromo-3-iodo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate

生成物 1

HCID 86693476Methyl 10-bromo-3-(2-(cyclopropanecarbonyl)hydrazinecarbonyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate収率 519.8%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

反応条件

温度
80 °C

実験手順

Methyl 10-bromo-3-iodo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate (100 mg, 0.2178 mmol) and cyclopropanecarbohydrazide (1.5 equiv., 34.43 mg, 0.3267 mmol) were dissolved in dry N,N-dimethylformamide (0.87 mL) and triethylamine (0.13 mL). The solution was sparged with nitrogen. Palladium(II) acetate (0.05 equiv., 2.5 mg, 0.01089 mmol) and xantphos (0.05000, 6.430 mg, 0.01089 mmol) were added and the solution was purged and fixed with a CO balloon. The reaction was heated to 80° C. for 2 h. The reaction was monitored by LC/MS for consumption of starting material. The reaction was cooled to room temperature and diluted with methylene chloride. Saturated aqueous sodium bicarbonate was added and the mixture was extracted twice with methylene chloride. The organic layers were combined, dried with sodium sulfate and concentrated. Purified by flash chromatography (10-100% EtOAc in heptanes) to afford 26 mg (26% yield) of a white solid.

後処理

  1. customThe solution was sparged with nitrogen
  2. customthe solution was purged
  3. customThe reaction was monitored by LC/MS for consumption of starting material
  4. temperatureThe reaction was cooled to room temperature
  5. additiondiluted with methylene chloride
  6. additionSaturated aqueous sodium bicarbonate was added
  7. extractionthe mixture was extracted twice with methylene chloride
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customPurified by flash chromatography (10-100% EtOAc in heptanes)

出典と根拠

ORDレコード
ord-ff67a407f97c4b9894a3c8f725759176
出典データセット
uspto-grants-2015_05
特許番号
US09034866B2

反応ノート

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