3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide → 3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide

HRID 2264959Notes

Reaction equation

HRID 2264959 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:20]([CH3:21])[C:19]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[C:13]=2[NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[O:11])[CH2:4][O:3]1>CO>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[N:20]([CH3:21])[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:13]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[F:30])=[O:11]

Participants

3

Reactant 1

HCID 595965023-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 249483223-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amideYield 18.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (71 mg, 0.13 mmol) was dissolved in methanol (0.5 ml) and loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was then washed with methanol (15 ml) and the desired product was subsequently eluted using 2M NH3 in MeOH. The eluant was collected and concentrated to give a residue. The residue was purified by flash chromatography (Si-PPC, dichloromethane:MeOH, gradient 100:0 to 90:10) followed by reversed phase HPLC (Phenomenex Luna 5 phenyl/hexyl, 0.1% TFA in water on a gradient of acetonitrile 100:0 to 40:60) to afford the title compound as a white solid (12 mg, 15%). LCMS (method A): RT=4.83 min, M+H+=501. 1H NMR (d4-MeOH, 400 MHz) 8.61 (s, 1H), 8.30 (d, J=6.0 Hz, 1H), 7.59 (d, J=6.0 Hz, 1H), 7.44 (dd, J=11.0 Hz, 1.8 Hz, 1H), 7.18-7.23 (m, 1H), 6.37 (dd, J=9.0 Hz, 9.0 Hz, 1H), 3.99 (s, 3H), 3.89-3.95 (m, 1H), 3.77-3.86 (m, 2H), 3.47-3.59 (m, 2H).

Workup

  1. washThe cartridge was then washed with methanol (15 ml)
  2. washthe desired product was subsequently eluted
  3. customThe eluant was collected
  4. concentrationconcentrated
  5. customto give a residue
  6. customThe residue was purified by flash chromatography (Si-PPC, dichloromethane:MeOH, gradient 100:0 to 90:10)

Sources & evidence

ORD record
ord-1da9062c7d384a16938083e5da75ecf0
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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