Iodine chloride → 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

HRID 2264950Notes

Reaction equation

HRID 2264950 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:13]([CH:14]2[CH2:16][CH2:15]2)[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([Si](C)(C)C)=[CH:20][C:19]=1[F:28])=[O:4].[I:29]Cl>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[N:13]([CH:14]2[CH2:16][CH2:15]2)[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([I:29])=[CH:20][C:19]=1[F:28])=[O:4]

Participants

4

Reactant 2

HCID 24640Iodine chlorideHCID 595964891-Cyclopropyl-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Product 1

HCID 595965401-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl esterYield 52.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-cyclopropyl-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (265.0 mg, 0.67 mmol) in anhydrous DCM at −10° C. was added iodine monochloride (1.0 M in DCM, 0.80 mL, 0.80 mmol, 1.2 eq). The reaction mixture was then stirred at ambient temperature for 15 minutes then quenched with saturated aqueous sodium thiosulfate solution (3 mL). The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous NaHCO3 solution, water, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (silica, ISCO, 45 mL/min, 25 to 100% ethyl acetate in hexane) to give the desired product as a yellow solid (159.0 mg, 52.9%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.53 (s, 1H), 8.33 (dd, J=6.0 Hz, J=1 Hz, 1H), 7.89 (s, 1H), 7.67-7.46 (m, 2H), 7.32 (m, 1H), 6.66 (dd, J=13.20 Hz, J=4.6 Hz, 1H), 3.81 (d, J=1.0 Hz, 3H), 3.61-3.41 (m, 1H), 1.22-1.10 (m, 2H), 0.90-0.79 (m, 2H); LC-MS (method C): [M+H]+=452.0, RT=0.79 min.

Workup

  1. customthen quenched with saturated aqueous sodium thiosulfate solution (3 mL)
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with saturated aqueous NaHCO3 solution, water, and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by flash column chromatography (silica, ISCO, 45 mL/min, 25 to 100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-845d624cf5bb4dc58de5954133a2a27d
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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