Dimethylformamide → HCID 67299125, compound

HRID 60240Notes

Reaction equation

HRID 60240 reaction equation
Cl[C:2]1[N:10]=[CH:9][C:8]2[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]3[N:19]=[CH:20][CH:21]=[CH:22][C:5]=3[C:4]=2[C:3]=1[F:23].[CH3:24][N:25](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:23][C:3]1[C:4]2[C:5]3[CH:22]=[CH:21][CH:20]=[N:19][C:6]=3[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:8]=2[CH:9]=[N:10][C:2]=1[C:24]#[N:25]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 583651946-Chloro-5-fluoro-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-pyrrolo[2,3-b:5,4-c']dipyridine

Product 1

HCID 67299125HCID 67299125, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
130 °C

Procedure

A solution of 6-chloro-5-fluoro-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′3′-d]pyrrole (12.2 g, 34.7 mmol) in DMF (120 mL) was treated with zinc cyanide (4.88 g, 41.7 mmol) and tetrakis(triphenylphosphine)palladium(0) (6 g, 5.2 mmol). The mixture was degassed and stirred under a nitrogen atmosphere at 130° C. for 3 hours. After cooling to ambient temperature the mixture was filtered through Celite© and the filter cake washed with DMF (10 mL). The filtrate was partitioned between ethyl acetate and water and the aqueous phase further extracted with ethyl acetate. The combined organic layer was washed with water (×2) and brine, dried (Na2SO4), filtered and evaporated. The resultant residue was dissolved in dichloromethane, stirred with flash silica gel, filtered to remove the solid and the solid washed well with dichloromethane. The filtrate was evaporated and the resultant residue triturated with pentane:diethyl ether (ca. 4:1) to afford the title compound as a white solid (8.15 g, 68%). The trituration liquors were evaporated and the resultant residue purified by flash chromatography to afford a second crop of title compound (0.92 g, 8%). Total yield=9.07 g, 76%. 1H NMR (400 MHz, CDCl3): 8.99 (d, J=2.1 Hz, 1H), 8.75 (dd, J=4.8, 1.7 Hz, 1H), 8.57 (dd, J=7.9, 1.7 Hz, 1H), 7.44 (dd, J=7.9, 4.8 Hz, 1H), 6.02 (s, 2H), 3.63-3.56 (m, 2H), 0.93 (t, J=8.2 Hz, 2H), −0.08 (d, J=0.6 Hz, 9H).

Workup

  1. customThe mixture was degassed
  2. temperatureAfter cooling to ambient temperature the mixture
  3. filtrationwas filtered through Celite©
  4. washthe filter cake washed with DMF (10 mL)
  5. customThe filtrate was partitioned between ethyl acetate and water
  6. extractionthe aqueous phase further extracted with ethyl acetate
  7. washThe combined organic layer was washed with water (×2) and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. dissolutionThe resultant residue was dissolved in dichloromethane
  12. stirringstirred with flash silica gel
  13. filtrationfiltered
  14. customto remove the solid
  15. washthe solid washed well with dichloromethane
  16. customThe filtrate was evaporated
  17. customthe resultant residue triturated with pentane

Sources & evidence

ORD record
ord-710e9dcd80514e7e86e68185766dfd01
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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