Benzophenone imine → HCID 86634843, compound

HRID 627901Notes

Reaction equation

HRID 627901 reaction equation
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:48]1[CH:49]=[CH:50][C:51]2[C:57]3[S:58][C:59]([C:61]([N:63]([C:65]4[CH:70]=[CH:69][CH:68]=[CH:67][C:66]=4[Cl:71])[CH3:64])=[O:62])=[CH:60][C:56]=3[CH2:55][CH2:54][O:53][C:52]=2[CH:72]=1.[C:73](=[NH:86])([C:80]1[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1)[C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1.CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:71][C:66]1[CH:67]=[CH:68][CH:69]=[CH:70][C:65]=1[N:63]([CH3:64])[C:61]([C:59]1[S:58][C:57]2[C:51]3[CH:50]=[CH:49][C:48]([N:86]=[C:73]([C:74]4[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=4)[C:80]4[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=4)=[CH:72][C:52]=3[O:53][CH2:54][CH2:55][C:56]=2[CH:60]=1)=[O:62]

Participants

7

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 442424278-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Product 1

HCID 86634843HCID 86634843, compoundYield 65.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Solid Pd2(dba)3 (101 mg, 0.11 mmol) and BINAP (205 mg, 0.33 mmol) was added to a 10 mL flask and the whole purged with nitrogen. To the flask was added 8-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (500 mg, 1.11 mmol), benzophenone imine (303 mg, 1.67 mmol), NaOtBu (213 mg, 2.22 mmol) and toluene (30 mL). The mixture was heated to 80° C. with stirring until the starting material had been consumed (determined by TLC analysis). The mixture was cooled to room temperature, diluted with EtOAc, filtered and concentrated. The crude product was purified by column chromatography (5:1 hexanes:ethyl acetate) to give N-(2-chlorophenyl)-8-(diphenylmethyleneamino)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide as a yellow solid (400 mg, yield 65%). N-(2-chlorophenyl)-8-(diphenylmethyleneamino)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (4.9 g, 8.92 mmol) was dissolved in 10 mL of MeOH. To the solution was added 6 mL of CH3COCl in MeOH (1:10). The mixture was stirred at room temperature for 15 min before concentrated under vacuum. The residue was washed with EtOAc to give 8-amino-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide as a white solid (3.6 g, yield 95%). 1H NMR (MeOD, 400 MHz): δ 7.59-6.60 (m, 8H), 4.21 (t, J=5.2 Hz, 2H), 3.31 (s, 3H), 2.96 (t, J=4.8 Hz, 2H).

Workup

  1. customthe whole purged with nitrogen
  2. customhad been consumed (determined by TLC analysis)
  3. temperatureThe mixture was cooled to room temperature
  4. additiondiluted with EtOAc
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (5:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-1ed47689cdea48788049c9d02bef0204
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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