Cyclohexylamine → HCID 66707052, compound

HRID 911736Notes

Reaction equation

HRID 911736 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.CC(C)([O-])C.[Na+].[CH:53]1([NH2:59])[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]1.[C:60]([O:64][C:65]([N:67]1[CH2:73][CH2:72][C:71]2[C:74]([S:79][CH2:80][C:81]3[CH:82]=[N:83][C:84](Cl)=[CH:85][CH:86]=3)=[C:75]([Cl:78])[CH:76]=[CH:77][C:70]=2[CH2:69][CH2:68]1)=[O:66])([CH3:63])([CH3:62])[CH3:61]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:60]([O:64][C:65]([N:67]1[CH2:73][CH2:72][C:71]2[C:74]([S:79][CH2:80][C:81]3[CH:82]=[N:83][C:84]([NH:59][CH:53]4[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]4)=[CH:85][CH:86]=3)=[C:75]([Cl:78])[CH:76]=[CH:77][C:70]=2[CH2:69][CH2:68]1)=[O:66])([CH3:63])([CH3:61])[CH3:62]

Participants

7

Reactant 4

HCID 7965CyclohexylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86629659HCID 86629659, compound

Product 1

HCID 66707052HCID 66707052, compoundYield 33.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Slurry palladium(II) acetate (434 mg, 1.9 mmol), BINAP (1.2 g, 1.9 mmol), sodium-tert-butoxide (644 mg, 6.7 mmol), cyclohexylamine (1.4 g, 14.4 mmol) and 3-tert-butoxycarbonyl-7-chloro-6-(6-chloro-pyridin-3-ylmethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (2.1 g, 4.8 mmol) in anhydrous toluene (70 mL). Degas the slurry under house vacuum, then buble nitrogen. Heat the mixture to 95° C. for 16 h under a nitrogen atmosphere. Cool the mixture to room temperature, dilute with EtOAc (50 mL) and filter through Celite®. Concentrate the filtrate to an oil and purify by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 13:7 gradient) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(6-cyclohexylamino-pyridin-3-ylmethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (800 mg, 33%). MS (ES+) m/z: 502.2 (M+H)+.

Workup

  1. customDegas the slurry under house vacuum
  2. temperatureCool the mixture to room temperature
  3. additiondilute with EtOAc (50 mL)
  4. filtrationfilter through Celite®
  5. concentrationConcentrate the filtrate to an oil
  6. custompurify by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 13:7 gradient)

Sources & evidence

ORD record
ord-93b06e88b498484280ff92c2b6de132a
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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