Sulfuric Acid → HCID 71209104, compound

HRID 1912601Notes

Reaction equation

HRID 1912601 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[F:22])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:18])=[C:13]([CH:16]=[O:17])[C:14]([I:15])=[C:9]2[CH:8]=[CH:7]1.[Si](C#N)(C)(C)C.S(=O)(=O)(O)O.[C:34]([O-:37])(O)=[O:35].[Na+].O.[C:40]([O-])(O)=O.[Na+]>C(Cl)Cl.[I-].[Zn+2].[I-]>[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[F:22])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:18])=[C:13]([CH:16]([OH:17])[C:34]([O:37][CH3:40])=[O:35])[C:14]([I:15])=[C:9]2[CH:8]=[CH:7]1

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 82115Trimethylsilyl cyanideHCID 516892Sodium BicarbonateHCID 86585896Sodium bicarbonate waterHCID 86675743HCID 86675743, compound

Product 1

HCID 71209104HCID 71209104, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (3.05 g, 6.29 mmol) in DCM (85 mL) at 0° C. was added zinc iodide (4.02 g, 12.58 mmol) followed by TMSCN (3.37 mL, 25.2 mmol) and the mixture was stirred at 0° C. for 5 min and then at RT for 30 min. The mixture was diluted with DCM and washed with cold water, dried (Na2SO4) and concentrated. The residue was cooled to 0° C. and MeOH (85 mL) was added followed by dropwise addition of sulfuric acid (16.09 mL, 302 mmol). The mixture was stirred at 80° C. for 26 h, cooled to 0° C. and saturated NaHCO3/water was added slowly followed by solid NaHCO3. The mixture extracted with EtOAc and washed with water, brine, dried (Na2 SO4), concentrated, dried in vacuo to provide methyl 2-(1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate (3.68 g, 6.23 mmol, 99% yield) as a thick yellowish oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.70 (s, 3 H), 3.47 (br s, 1 H), 3.81 (s, 3 H), 5.42-5.59 (m, 2H), 5.91 (s, 1 H), 6.41 (d, J=3.52 Hz, 1H), 6.93-7.22 (m, 3 H); LCMS (m/z) ES+=473 (M+1).

Workup

  1. waitat RT for 30 min
  2. washwashed with cold water
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. temperatureThe residue was cooled to 0° C.
  6. additionMeOH (85 mL) was added
  7. stirringThe mixture was stirred at 80° C. for 26 h
  8. temperaturecooled to 0° C.
  9. extractionThe mixture extracted with EtOAc
  10. washwashed with water, brine
  11. customdried (Na2 SO4)
  12. concentrationconcentrated
  13. customdried in vacuo

Sources & evidence

ORD record
ord-cd49aab95b974ed18c7584f26998155f
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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