Dimethylformamide → HCID 86710410, compound

HRID 1398421Notes

Reaction equation

HRID 1398421 reaction equation
Br[C:2]1[C:18]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14].[CH3:34][N:35](C=O)C>O.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[Zn+2].[C-]#N>[C:34]([C:2]1[C:18]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14])#[N:35]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 86710370HCID 86710370, compound

Product 1

HCID 86710410HCID 86710410, compoundYield 88%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of (S)-tert-butyl (1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (2.4 g, 4.63 mmol), prepared as described in Example 3, Part A, Pd2(dba)3 (0.212 g, 0.231 mmol), DPPF (0.257 g, 0.463 mmol) and zinc(II) cyanide (0.544 g, 4.63 mmol) in DMF (20 mL) and water (1 mL) was degassed with nitrogen and heated to 130° C. overnight. Ater cooling to room temperature, the volatiles were concentrated under reduced pressure. The residue was reconstituted in ethyl acetate and filtered through diatomaceous earth (Celite®). The organic layer was washed with H2O, followed by brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column (petroleum ether and ethyl acetate) to afford (S)-tert-butyl 1-(9-cyano-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (1.9 g, 4.09 mmol, 88% yield) as a yellow solid. LC/MS (ESI) m/e 465.2 [(M+H)+, calcd for C26H33N4O4, 465.2]; LC/MS retention time (method C): tR=2.74 min.

Workup

  1. customprepared
  2. customwas degassed with nitrogen
  3. temperatureAter cooling to room temperature
  4. concentrationthe volatiles were concentrated under reduced pressure
  5. filtrationfiltered through diatomaceous earth (Celite®)
  6. washThe organic layer was washed with H2O
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by silica gel column (petroleum ether and ethyl acetate)

Sources & evidence

ORD record
ord-737f59387eb74ed5862e1bf5e6f0c8ff
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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