Nitrogen → 10-Bromo-9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530700ノート

反応式

HRID 1530700 の反応式
[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11](I)=[CH:10]3)=[CH:4][C:3]=1[F:17].Cl.C(N)(=N)C.[CH2:23]([N:25](CC)[CH2:26]C)[CH3:24].N#N.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.Cl.[CH:75]([NH:78][NH2:79])([CH3:77])[CH3:76]>CN(C)C=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(=O)C>[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:26]2[N:78]([CH:75]([CH3:77])[CH3:76])[N:79]=[C:23]([CH3:24])[N:25]=2)=[CH:10]3)=[CH:4][C:3]=1[F:17]

参加物

11

反応物 6

HCID 947NitrogenHCID 8471TriethylamineHCID 67170Acetamidine monohydrochlorideHCID 855731-Isopropylhydrazine hydrochlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6831272510-Bromo-9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

生成物 1

HCID 6831287410-Bromo-9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine収率 50%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
40 °C

実験手順

A solution of 13-bromo-4-iodo-12-fluoro-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (10.0 g, 24.4 mmol) and acetamidine hydrochloride (2.63 g, 26.9 mmol) in triethylamine (6.90 mL, 49.4 mmol) and N,N-dimethylformamide (32.0 mL) was thoroughly degassed with N2. Palladium acetate (276 mg, 1.22 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.40 g, 2.44 mmol) were added and the solution was degassed with CO for 1 minute. A CO balloon was attached to the flask and the reaction was heated to 40° C. for 2 h. After being cooled to room temperature, the mixture was further treated with isopropylhydrazine hydrochloride (4.05 g, 36.6 mmol) and acetic acid (15 mL). The resulting mixture was heated again to 80° C. for 1 h. After cooling to room temperature, the mixture was diluted with H2O (400 mL). The resulting solid was collected by filtration and purified by silica gel chromatography using 15-50% EtOAc in petroleum ether as eluant to give the title compound (4.9 g, 50% yield). LCMS m/z [M+H]+ 406.0.

後処理

  1. customthe solution was degassed with CO for 1 minute
  2. temperatureAfter being cooled to room temperature
  3. temperatureThe resulting mixture was heated again to 80° C. for 1 h
  4. temperatureAfter cooling to room temperature
  5. filtrationThe resulting solid was collected by filtration
  6. custompurified by silica gel chromatography

出典と根拠

ORDレコード
ord-089fc55ee82c46e2895a164635c463ba
出典データセット
uspto-grants-2015_07
特許番号
US09090628B2

反応ノート

読み込み中…