Dimethylformamide → HCID 70981213, compound

HRID 2280762Notes

Reaction equation

HRID 2280762 reaction equation
Br[C:2]1[C:3]([S:13][CH3:14])=[N:4][C:5]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[N:6][CH:7]=1.[CH3:15][N:16](C=O)C>C(OCC)(=O)C.O.[Zn].[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+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:9]([NH:8][C:5]1[N:4]=[C:3]([S:13][CH3:14])[C:2]([C:15]#[N:16])=[CH:7][N:6]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

9

Reactant 2

HCID 6228DimethylformamideHCID 70981713HCID 70981713, compound

Product 1

HCID 70981213HCID 70981213, compoundYield 83%

Reagents, catalysts & solvents 6

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-N-tert-butyl-4-(methylthio)pyrimidin-2-amine (3400 mg, 12.31 mmol), zinc dust (201 mg, 3.08 mmol), zinc cyanide (940 mg, 8.00 mmol), 1,1′-bis-(diphenylphosphino)-ferrocene (552 mg, 0.985 mmol), tris(dibenzylideneacetone)dipalladium(0) (564 mg, 0.616 mmol), and DMF (20.5 mL) were combined and heated at 90° C. overnight under nitrogen. The reaction mixture was diluted with 125 mL ethyl acetate and 50 mL of water and then filtered through a pad of Celite. The layers of filtrate were separated and the aqueous layer was extracted with 75 mL ethyl acetate. The combined ethyl acetate layers were washed with 2×50 mL brine, dried over anhydrous magnesium sulfate, filtered and concentrated to an oil under reduced pressure. The crude oil was purified by silica gel chromatography (0-30% ethyl acetate/hexane) to afford 2-(tert-butylamino)-4-(methylthio)pyrimidine-5-carbonitrile (2.26 g, 10.17 mmol, 83% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.37-8.51 (m, 1H), 7.85-8.10 (m, 1H), 2.53-2.62 (m, 3H), 1.41 (s, 9H). MS (ESI) m/z 223.1 [M+1]+.

Workup

  1. filtrationfiltered through a pad of Celite
  2. customThe layers of filtrate were separated
  3. extractionthe aqueous layer was extracted with 75 mL ethyl acetate
  4. washThe combined ethyl acetate layers were washed with 2×50 mL brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to an oil under reduced pressure
  8. customThe crude oil was purified by silica gel chromatography (0-30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a992045408ba49848047d5359e6a1cbb
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

Loading…