Nitrogen → HCID 118061472, compound

HRID 920798Notes

Reaction equation

HRID 920798 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]([O:16][CH3:17])=[O:15])[CH2:11][C:10]([F:13])([F:12])[CH2:9]2)=[CH:4][CH:3]=1.N#N.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH3:49][N:50](C=O)C>O.[C-]#N.[C-]#N.[Zn+2].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]>[C:49]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]([O:16][CH3:17])=[O:15])[CH2:11][C:10]([F:13])([F:12])[CH2:9]2)=[CH:4][CH:3]=1)#[N:50]

Participants

8

Reactant 4

HCID 947NitrogenHCID 6228DimethylformamideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 118062965HCID 118062965, compound

Product 1

HCID 118061472HCID 118061472, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of Intermediate 314D (500 mg, 1.639 mmol) in DMF (10 mL) was added Zn(CN)2 (289 mg, 2.458 mmol) and the reaction mixture was degassed with N2 gas for 15 min Pd2(dba)3 (75 mg, 0.082 mmol) and dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (67.3 mg, 0.164 mmol) were then added and the reaction mixture was heated at 120° C. for 1 h. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with EtOAc (3×40 mL) The combined organic layer was washed with water, brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 10% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford Intermediate 314E as a colorless liquid (350 mg, 85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.87 (d, J=8.5 Hz, 2H), 7.58 (d, J=8.5 Hz, 2H), 3.62 (s, 3H), 3.51-3.37 (m, 2H), 3.28-3.13 (m, 2H).

Workup

  1. additionwere then added
  2. temperatureThe reaction mixture was cooled to RT
  3. extractionextracted with EtOAc (3×40 mL) The combined organic layer
  4. washwas washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated
  8. customThe crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 10% EtOAc in hexane)
  9. additionFractions containing the product
  10. customevaporated

Sources & evidence

ORD record
ord-6366a3e408b8451eb968a84e5015da95
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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