Hydrochloric Acid → HCID 71209351, compound

HRID 1912598Notes

Reaction equation

HRID 1912598 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:21])=[C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:14](O)=[C:9]2[CH:8]=[CH:7]1.N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[I-:47].[Na+].Cl.C([O-])(O)=O.[Na+].O>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:21])=[C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:14]([I:47])=[C:9]2[CH:8]=[CH:7]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 5238Sodium IodideHCID 67749Trifluoromethanesulfonic anhydrideHCID 86585896Sodium bicarbonate waterHCID 178469183HCID 178469183, compound

Product 1

HCID 71209351HCID 71209351, compoundYield 92.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 1-(3,4-difluorobenzyl)-4-hydroxy-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (5.0 g, 13.7 mmol) in acetonitrile (100 mL) was added pyridine (1.3 mL, 15.77 mmol) and the mixture was cooled to 0° C. and triflic anhydride (2.55 mL, 15.09 mmol) was added dropwise in ˜10 min. The mixture was stirred at RT for 1 h then charged with sodium iodide (10.28 g, 68.6 mmol) in one portion followed by dropwise addition of hydrochloric acid (7.54 mL, 15.09 mmol) (2 M/water). The mixture was stirred at 60° C. for 2 h. Saturated NaHCO3/water was carefully added and the mixture was concentrated and then partitioned between EtOAc and water. The organic phase was washed with satd. Na2S2O3/water, saturated NaHCO3/water, brine, dried (Na2SO4), concentrated to provide ethyl 1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (6.5 g, 12.68 mmol, 92% yield) as a dark oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46 (t, J=7 Hz, 3 H), 2.65 (s, 3 H), 4.48 (q, J=7 Hz, 2 H), 5.39 (s, 2 H), 6.39 (d, J=3.71 Hz, 1 H), 6.86-7.14 (m, 3 H), 7.17 (d, J=3.71 Hz, 1 H); LCMS (m/z) ES+=457 (M+1).

Workup

  1. stirringThe mixture was stirred at 60° C. for 2 h
  2. concentrationthe mixture was concentrated
  3. custompartitioned between EtOAc and water
  4. washThe organic phase was washed with satd
  5. dry with materialNa2S2O3/water, saturated NaHCO3/water, brine, dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c7dfa084ffe5432b984d435c1a77bd0e
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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