Ethyl Acetate → 7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine-2-carbonitrile

HRID 1262400Notes

Reaction equation

HRID 1262400 reaction equation
CS([C:5]1[N:10]=[CH:9][C:8]2=[CH:11][CH:12]=[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])[N:7]2[N:6]=1)(=O)=O.[C-]#N.[K+].[CH3:25][N:26]1CCCC1=O.CCOC(C)=O>CO.C(Cl)Cl>[CH3:21][O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:13]1[N:7]2[C:8]([CH:9]=[N:10][C:5]([C:25]#[N:26])=[N:6]2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 9032Potassium CyanideHCID 13387N-methyl-2-pyrrolidoneHCID 667123212-Methanesulfonyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 667124197-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine-2-carbonitrileYield 72.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

2-Methanesulfonyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (804 mg, 2.65 mmol) and Potassium cyanide (311 mg, 4.77 mmol) in N-Methylpyrrolidinone (8.0 mL, 84 mmol) was stirred under an atmosphere of Nitrogen at 80° C. for 7 h, reaching ˜90% conversion. Work up by partitioning between 50% brine (40 mL):EtOAc (60 mL); giving an emulsion, so DCM (20 mL) was added. The emulsion did not successfully break, so it was kept with the aq. The aq. and emulsion was ext. with EtOAc (3×40 mL), the emulsion was isolated by itself and solubilized with DCM:MeOH. Combining all the org. layers, the mix. was washed with satd. NaHCO3 (50 mL) and brine (2×50 mL), dried over sodium sulfate (two iterations) then conc. in vacuo. Purify on silica gel (ISCO 40 g, 0-40% EtOAc:Hex) to afford 7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine-2-carbonitrile (0.480 g, 72%). 1H-NMR (CDCl3): 8.95 (s, 1H), 7.73 (m, 1H), 7.48 (m, 1H), 7.42 (d, 1H, J=4.7 Hz), 7.1-7.2 (m, 3H), 3.87 (s, 3H).

Workup

  1. customby partitioning between 50% brine (40 mL)
  2. customgiving an emulsion, so DCM (20 mL)
  3. additionwas added
  4. washwas washed with satd
  5. dry with materialNaHCO3 (50 mL) and brine (2×50 mL), dried over sodium sulfate (two iterations)
  6. customPurify on silica gel (ISCO 40 g, 0-40% EtOAc:Hex)

Sources & evidence

ORD record
ord-9c4dea06c06641e29bdde376ab80040c
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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