Sodium Hydroxide → 3-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2264964Notes

Reaction equation

HRID 2264964 reaction equation
CO[C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:27][C:28]1[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=1[F:35])=[O:4].[OH-].[Na+].[CH:38]([O:40][CH2:41][CH2:42][O:43][NH2:44])=[CH2:39].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(O)C.C1COCC1>[CH:38]([O:40][CH2:41][CH2:42][O:43][NH:44][C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:18]([CH3:19])[CH3:20])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:22])[CH3:23])[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:27][C:28]1[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=1[F:35])=[O:4])=[CH2:39]

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 595965243-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Product 1

HCID 595966633-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a suspension of 3-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (90 mg, 0.15 mmol) in ethanol (2 mL) was added a 1M aqueous solution of sodium hydroxide (0.15 mL, 0.15 mmol). The reaction mixture was heated at 65° C., stirred for 1 hour, cooled to room temperature, concentrated and azeotroped with toluene. The resultant residue was suspended in THF to which O-(2-vinyloxy-ethyl)-hydroxylamine (31 mg, 0.30 mmol), EDCI (37 mg, 0.19 mmol), HOBt (30 mg, 0.22 mmol) and DIPEA (105 μl, 0.60 mmol) were added. The reaction mixture was stirred at room temperature for 16 h then concentrated to give a residue which was purified by flash chromatography (Si-PPC, cyclohexane:EtOAc, gradient 100:0 to 0:100). The title compound was obtained as a yellow solid (58 mg, 57%). LCMS (method B): RT=3.24 min, M+H+=683.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customazeotroped with toluene
  4. additionwere added
  5. stirringThe reaction mixture was stirred at room temperature for 16 h
  6. concentrationthen concentrated
  7. customto give a residue which
  8. customwas purified by flash chromatography (Si-PPC, cyclohexane:EtOAc, gradient 100:0 to 0:100)

Sources & evidence

ORD record
ord-7f770d92c72b4e2aaed5969809ff760d
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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