Triethylamine → N-((4-(Dibenzo[b,f][1,4]thiazepin-11-yl)-1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)-2,2,2-trifluoroacetamide

HRID 625177Notes

Reaction equation

HRID 625177 reaction equation
Cl[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[S:6][C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=1.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.C(N(CC)CC)C.[F:70][C:71]([F:89])([F:88])[C:72]([NH:74][CH2:75][CH:76]1[CH2:81][NH:80][CH2:79][CH2:78][N:77]1[CH2:82][CH2:83][O:84][CH2:85][CH2:86][OH:87])=[O:73]>O1CCOCC1.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]>[CH:9]1[C:8]2[C:2]([N:80]3[CH2:79][CH2:78][N:77]([CH2:82][CH2:83][O:84][CH2:85][CH2:86][OH:87])[CH:76]([CH2:75][NH:74][C:72](=[O:73])[C:71]([F:89])([F:88])[F:70])[CH2:81]3)=[N:3][C:4]3[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=3[S:6][C:7]=2[CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 634876Binap, (A+-)-HCID 1058648111-Chlorodibenzo(b,f)(1,4)thiazepineHCID 867111502,2,2-Trifluoro-N-((1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)acetamide

Product 1

HCID 86711152N-((4-(Dibenzo[b,f][1,4]thiazepin-11-yl)-1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)-2,2,2-trifluoroacetamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 11-chlorodibenzo[b,f][1,4]thiazepine, prepared as described in the previous step, (2 g, crude) in dioxane (20 mL) was added Pd2(dba)3 (327 mg, 0.357 mmol), BINAP (225 mg, 0.357 mmol), triethylamine (6 mL, 42.9 mmol) and 2,2,2-trifluoro-N-((1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)acetamide, prepared as described as Step F, (2.4 g, crude). The resulting mixture was heated to reflux overnight under nitrogen atmosphere, filtered through CELITE™, and concentrated. The residue was purified by silica gel chromatography to provide the title compound. ESI-MS (M+1): 509 calc. for C24H27F3N4O3S 508.

Workup

  1. customprepared
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux overnight under nitrogen atmosphere
  4. filtrationfiltered through CELITE™
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-113f5628de674dd183634be2cd94789b
Source dataset
uspto-grants-2016_04
Patent number
US09304126B2

Reaction notes

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