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 1530700노트

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HRID 1530700 반응식
[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]

참가 물질

11

반응물 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

생성물 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]oxazepine수율 50%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 176Acetic Acid용매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
40 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-089fc55ee82c46e2895a164635c463ba
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090628B2

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