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 1530700Notes

Reaction equation

HRID 1530700 reaction equation
[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]

Participants

11

Reactant 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

Product 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]oxazepineYield 50%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-089fc55ee82c46e2895a164635c463ba
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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