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

HRID 2264909Notes

Reaction equation

HRID 2264909 reaction equation
[I:1]Cl.[CH3:3][O:4][C:5]([C:7]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:14]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[C:8]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([Si](C)(C)C)=[CH:28][C:27]=1[F:36])=[O:6]>C(Cl)Cl>[CH3:3][O:4][C:5]([C:7]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:14]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[C:8]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([I:1])=[CH:28][C:27]=1[F:36])=[O:6]

Participants

4

Reactant 2

HCID 24640Iodine chlorideHCID 595966493-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Product 1

HCID 595966563-(2-Fluoro-4-iodo-phenylamino)-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Iodine monochloride (1M in DCM, 1.13 mL) was added dropwise over 10 minutes to a cooled (−10° C.) solution of 3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (269 mg, 0.56 mmol) in DCM (5 mL). The mixture was allowed to warm to ambient temperature and stirred for 20 minutes then quenched by the addition of saturated sodium thiosulphate solution (1 mL). The solution was partitioned between DCM (30 mL) and water (20 mL), the organic layer was separated, dried (Na2SO4), filtered and evaporated to give an orange oil. The oil was purified by flash column chromatography on silica (Si-PPC, cyclohexane:EtOAc, gradient 90:10 to 40:60) to provide the title compound as a yellow solid (240 mg, 80%). LCMS (method B): RT=2.59 min, M+H+=532.

Workup

  1. customthen quenched by the addition of saturated sodium thiosulphate solution (1 mL)
  2. customThe solution was partitioned between DCM (30 mL) and water (20 mL)
  3. customthe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give an orange oil
  8. customThe oil was purified by flash column chromatography on silica (Si-PPC, cyclohexane:EtOAc, gradient 90:10 to 40:60)

Sources & evidence

ORD record
ord-cfffedff16df48c5b2bc2c6f6dab5562
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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