Sodium Hydroxide → 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

HRID 2264958Notes

Reaction equation

HRID 2264958 reaction equation
C(O[C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:5])C.[OH-].[Na+].[CH3:27][C:28]1([CH3:36])[O:32][C@@H:31]([CH2:33][O:34][NH2:35])[CH2:30][O:29]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C1COCC1.C(O)C>[CH3:27][C:28]1([CH3:36])[O:32][C@@H:31]([CH2:33][O:34][NH:35][C:4]([C:6]2[N:14]([CH3:15])[C:13]3[CH:12]=[CH:11][N:10]=[CH:9][C:8]=3[C:7]=2[NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[O:5])[CH2:30][O:29]1

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11298047(R)-O-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)hydroxylamineHCID 595965873-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 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)-amideYield 65%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 3-(2-fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (90 mg, 0.21 mmol), 1N aqueous NaOH solution (0.22 ml, 0.22 mmol) and ethanol (3 ml) were heated at 65° C. for 2.5 hours. The reaction mixture was concentrated and then azeotroped with toluene (2×5 ml) to give a solid residue. The solid residue was dissolved in anhydrous THF (5 ml) and O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)hydroxylamine (49 mg, 0.41 mmol), EDCI (49 mg, 0.26 mmol), HOBt (39 mg, 0.29 mmol) and DIPEA (109 μl, 0.62 mmol) were added. After stirring for 19 hours the solvent was evaporated and the residue was partitioned between ethyl acetate (30 ml) and water (20 ml). The organic layer was isolated, dried over sodium sulphate then filtered and evaporated to give a yellow oil. The oil was purified by flash chromatography (Si-PPC, pentane:ethyl acetate, gradient 50:50 to 0:100) to afford the title compound as a yellow solid (71 mg, 65%). LCMS (method B): RT=2.87 min, M+H+=542.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customazeotroped with toluene (2×5 ml)
  3. customto give a solid residue
  4. customwas evaporated
  5. customthe residue was partitioned between ethyl acetate (30 ml) and water (20 ml)
  6. customThe organic layer was isolated
  7. dry with materialdried over sodium sulphate
  8. filtrationthen filtered
  9. customevaporated
  10. customto give a yellow oil
  11. customThe oil was purified by flash chromatography (Si-PPC, pentane:ethyl acetate, gradient 50:50 to 0:100)

Sources & evidence

ORD record
ord-74c5b384a28c4f61bf2510874f6fd832
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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