N-Methyl dicyclohexylamine → HCID 86723418, compound

HRID 2201174Notes

Reaction equation

HRID 2201174 reaction equation
[CH3:1][N:2]1[C:7]2=[C:8]3[N:13]([C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)=[C:6]2[C:5](=[O:21])[N:4]([CH3:22])[C:3]1=[O:23])[CH2:12][CH2:11][CH:10]=[CH:9]3.Br[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=1[F:32].C1(N(C)C2CCCCC2)CCCCC1>CC(N(C)C)=O.CCOC(C)=O.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.Cl[Pd]Cl.[Fe]>[F:31][C:27]1[C:26]([F:32])=[CH:25][CH:30]=[CH:29][C:28]=1[C:9]1[C:8]2[N:13]([C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:6]3[C:5](=[O:21])[N:4]([CH3:22])[C:3](=[O:23])[N:2]([CH3:1])[C:7]3=2)[CH2:12][CH2:11][CH:10]=1

Participants

7

Reactant 3

HCID 24210N-Methyl dicyclohexylamineHCID 27332601-Bromo-2,3-difluorobenzene3×HCID 86723419HCID 86723419, compound2×

Product 1

HCID 86723418HCID 86723418, compound

Reagents, catalysts & solvents 3

HCID 178454869HCID 178454869, compoundCatalyst3×HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

1,3-Dimethyl-5-phenyl-7,8-dihydropyrimido[4,5-a]indolizine-2,4(1H,3H)-dione (Intermediate I) (180 mg, 0.586 mmol), 1-bromo-2,3-difluorobenzene (commercially available) (0.085 mL, 0.761 mmol) and N-cyclohexyl-N-methylcyclohexanamine (commercially available) (0.251 mL, 1.171 mmol) were combined in DMA (2.5 mL) and the mixture sparged with nitrogen for 30 min. [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (commercially available) (38.2 mg, 0.059 mmol) was then added and the mixture heated at 110° C. for 1 hour under microwave irradiation. After cooling to room temperature, the mixture was heated at 110° C. for a further 6 hours. Further portions of 1-bromo-2,3-difluorobenzene (0.085 mL, 0.761 mmol) and [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (38.2 mg, 0.059 mmol) were added, and the mixture heated at 110° C. for a further 5 h. Further [1,1′-Bis(di-tert-butylphosphino) ferrocene]dichloropalladium(II) (38.2 mg, 0.059 mmol) and 1-bromo-2,3-difluorobenzene (0.085 mL, 0.761 mmol) were added and the mixture heated 110° C. for a further 6 hours. Further [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (38.2 mg, 0.059 mmol) was added and the mixture heated at 110° C. for a further 6 h. The reaction mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried over sodium sulphate and evaporated under reduced pressure. Purification by chromatography on silica, eluting with 15% EtOAc in iso-hexane afforded the title compound, which was used without further purification.

Workup

  1. customthe mixture sparged with nitrogen for 30 min. [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (commercially available) (38.2 mg, 0.059 mmol)
  2. additionwas then added
  3. temperatureAfter cooling to room temperature
  4. temperaturethe mixture was heated at 110° C. for a further 6 hours
  5. temperaturethe mixture heated at 110° C. for a further 5 h
  6. temperaturethe mixture heated 110° C. for a further 6 hours
  7. temperaturethe mixture heated at 110° C. for a further 6 h
  8. washwashed with water and brine
  9. dry with materialThe organic phase was dried over sodium sulphate
  10. customevaporated under reduced pressure
  11. customPurification by chromatography on silica
  12. washeluting with 15% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-c5c04203eb324fb2b713abb9b549cb5c
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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