Hydrochloric Acid → 3-(2-Fluoro-4-iodo-phenylamino)-1-prop-2-ynyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 2264979Notes

Reaction equation

HRID 2264979 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:18]([CH2:19][C:20]#[CH:21])[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[F:30])=[O:9])=C.Cl.O1CCOCC1>CO.C1COCC1>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:18]([CH2:19][C:20]#[CH:21])[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[F:30])=[O:9]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 595966543-(2-Fluoro-4-iodo-phenylamino)-1-prop-2-ynyl-1-H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 595965553-(2-Fluoro-4-iodo-phenylamino)-1-prop-2-ynyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-ethoxy)-amideYield 98.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(2-fluoro-4-iodo-phenylamino)-1-prop-2-ynyl-1-H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide (35.0 mg, 0.067 mmol) in anhydrous MeOH (6.7 mL) and anhydrous THF (3.4 mL) under N2 was added 4 M HCl in dioxane (50 μL, 0.20 mmol, 3.0 eq), and the reaction mixture was stirred at room temperature. After 3 h the solvent was removed in vacuo and the residue was redissolved in acetonitrile (2.0 mL) and loaded onto Phenomenex Strata-X cartridge (5 g). The cartridge was washed with water (10 mL) and MeOH (15 ml). The desired product was then eluted using 2M ammonia in MeOH. Trituration from DCM-hexane afforded the title compound as a yellow solid (32.7 mg, 98.5%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.58 (d, J=0.82 Hz, 1H), 8.36 (d, J=5.93 Hz, 1H), 7.79-7.62 (m, 2H), 7.60-7.47 (m, 1H), 7.30-7.15 (m, 1H), 6.34-6.15 (m, 1H), 5.33 (s, 2H), 4.77 (broad s, 1H), 3.84 (t, J=4.54 Hz, 2H), 3.61-3.50 (m, 2H), 3.42-3.34 (m, 2H); LC-MS (method E): [M+H]+=495.1, RT=3.54 min.

Workup

  1. customAfter 3 h the solvent was removed in vacuo
  2. dissolutionthe residue was redissolved in acetonitrile (2.0 mL)
  3. washThe cartridge was washed with water (10 mL) and MeOH (15 ml)
  4. washThe desired product was then eluted

Sources & evidence

ORD record
ord-3662101be87345589118f01f65e11f98
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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