Ammonium Chloride → 10-bromo-3-cyclopropyl-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

HRID 575470ノート

反応式

HRID 575470 の反応式
[Br:1][C:2]1[C:3]([F:21])=[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]([NH2:18])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:20]=1.[Br-].[CH:23]1([Zn+])[CH2:25][CH2:24]1.[Cl-].[NH4+]>CC(N(C)C)=O.O.[Zn]>[Br:1][C:2]1[C:3]([F:21])=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[C:13]([CH:23]4[CH2:25][CH2:24]4)=[C:14]([C:16]([NH2:18])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:20]=1

参加物

7

反応物 3

HCID 25517Ammonium ChlorideHCID 8669308210-bromo-9-fluoro-3-iodo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamideHCID 178419765HCID 178419765、化合物

生成物 1

HCID 8669353710-bromo-3-cyclopropyl-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

試薬・触媒・溶媒 3

HCID 23994Zinc触媒2 回HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

実験手順

A solution of 10-bromo-9-fluoro-3-iodo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide (2.0 g, 4.3 mmol) in 15 mL dry DMA with PdCl2-[P(o-Tol)3]2 (210 mg, 0.26 mmol) was sparged with nitrogen gas then treated with a solution of cyclopropylzinc bromide (19 mL, 9.5 mmol, 0.5 M in THF) over 10 min. The mixture was heated at 50° C. for 40 min at which time 10 mL of additional zinc reagent (5 mmols, 1.16 eq) was added at 50° C. with sparging nitrogen. After 15 min, an additional 6 mL of zinc reagent was added. The mixture was cooled to room temp and treated with ˜5 mL of ammonium chloride. The mixture was diluted with water and extracted with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate and concentrated by rotoevaporation. The mixture was dissolved in DMF and purified by RPHPLC. The resultant solid was used in subsequent operations without further purification.

後処理

  1. additionwas added at 50° C. with sparging nitrogen
  2. extractionextracted with ethyl acetate
  3. washThe combined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated by rotoevaporation
  6. dissolutionThe mixture was dissolved in DMF
  7. custompurified by RPHPLC
  8. customThe resultant solid was used in subsequent operations without further purification

出典と根拠

ORDレコード
ord-2d5b1237ed85445d9dc0e22846d1ff3c
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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