Sodium Hydroxide → HCID 59596464, compound

HRID 2264960Notes

Reaction equation

HRID 2264960 reaction equation
C(O[C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[C:9](CC)[C:8]=2[C:7]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])=[O:5])C.[OH-].[Na+].[CH:29]([O:31][CH2:32][CH2:33][O:34][NH2:35])=[CH2:30].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C1COCC1.CO>[CH:29]([O:31][CH2:32][CH2:33][O:34][NH:35][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:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])=[O:5])=[CH2:30]

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 67212327HCID 67212327, compound

Product 1

HCID 59596464HCID 59596464, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of ethyl 3-(2-fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (100 mg, 0.23 mmol), 1N aqueous sodium hydroxide (0.25 ml) and MeOH (3.0 ml) was heated at 65° C. for 1.5 hours. The reaction mixture was concentrated and azeotroped with toluene (2×2 ml) to give a solid residue. The solid residue was dissolved in anhydrous THF (4 ml) and O-(2-vinyloxy-ethyl)-hydroxylamine (47 mg, 0.46 mmol), EDCI (55 mg, 0.29 mmol), HOBt (43 mg, 0.32 mmol) and DIPEA (119 μl, 0.68 mmol) were added. After stirring for 72 hours at ambient temperature, the mixture 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, dichloromethane:methanol, gradient 100:0 to 90:10) to afford the title compound as a yellow solid (64 mg, 57%). LCMS (method B): RT=2.20 min, M+H+=497.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customazeotroped with toluene (2×2 ml)
  3. customto give a solid residue
  4. customthe mixture was 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. filtrationfiltered
  9. customevaporated
  10. customto give a yellow oil
  11. customThe oil was purified by flash chromatography (Si-PPC, dichloromethane:methanol, gradient 100:0 to 90:10)

Sources & evidence

ORD record
ord-7c0f11d6811049da82a97cc7130e6484
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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