Nitrogen → tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate

HRID 593443Notes

Reaction equation

HRID 593443 reaction equation
C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:9]=[CH:10][C:11]2=[C:12]([CH:35]=1)[N:13]=[C:14]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:15][C:16]([C:18](=[O:26])[N:19]([CH2:23][CH2:24][CH3:25])[CH2:20][CH2:21][CH3:22])=[CH:17]2.O.[K].[K].C1(P(C2C=CC(S(O)(=O)=O)=CC=2)C2C=CC(S(O)(=O)=O)=CC=2)C=CC=CC=1.N#N.[CH3:68][N:69]([CH3:81])[C:70]([C:72]1[CH:77]=[CH:76][C:75](B(O)O)=[CH:74][CH:73]=1)=[O:71]>CCO.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:68][N:69]([CH3:81])[C:70]([C:72]1[CH:77]=[CH:76][C:75]([C:8]2[CH:9]=[CH:10][C:11]3=[C:12]([CH:35]=2)[N:13]=[C:14]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH2:15][C:16]([C:18](=[O:26])[N:19]([CH2:20][CH2:21][CH3:22])[CH2:23][CH2:24][CH3:25])=[CH:17]3)=[CH:74][CH:73]=1)=[O:71]

Participants

10

Reactant 5

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 35037674-(Dimethylcarbamoyl)phenylboronic AcidHCID 46928349tert-Butyl (8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-yl)carbamateHCID 866526824,4'-(Phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate

Product 1

HCID 86653475tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamateYield 83.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolvent2×HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To Na2CO3 (129 mg, 1.214 mmol) in a 50 mL round-bottom flask was added water (3.7 mL) was bubbled with N2 for 10 min. To this mixture was added tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate (200 mg, 0.40 mmol) in EtOH (4.9 mL) at room temperature. The resulting mixture was bubbled with N2 for 10 min. Pd(OAc)2 (9.3 mg, 0.040 mmol) and 4,4′-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (45 mg, 0.081 mmol) were added. The resulting mixture was warmed to 65° C. with N2 bubbling. To this mixture was added a solution of 4-(dimethylcarbamoyl)phenylboronic acid (97 mg, 0.49 mmol) in EtOH (0.6 mL). The resulting mixture was stirred at 65° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give the crude material that was diluted with water (5 mL) and EtOAc (10 mL). The mixture was filtered through GF/F filter. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude product that was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2) to afford 178 mg (83%) of tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate. MS APCI(+) m/z 533 (M+1) detected.

Workup

  1. customwas bubbled with N2 for 10 min
  2. customThe resulting mixture was bubbled with N2 for 10 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude material that
  6. filtrationThe mixture was filtered through GF/F
  7. filtrationfilter
  8. customThe aqueous layer was separated
  9. extractionextracted with EtOAc (10 mL)
  10. washThe combined organic layers were washed with brine (10 mL)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto give the crude product that
  15. customwas purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9e1bc356b024450f9fb690cd636730f4
Source dataset
uspto-grants-2016_01
Patent number
US09242964B2

Reaction notes

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