HCID 86656242, compound → 4-(2-Fluoro-4-iodophenylamino)-1H-pyrazolo[3,4-b]pyridine 5-carboxylic acid (2-hydroxyethoxy)-amide

HRID 79053Notes

Reaction equation

HRID 79053 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[C:11]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=2[F:36])=[C:12]2[CH:18]=[N:17][N:16](CC3C=CC(OC)=CC=3)[C:13]2=[N:14][CH:15]=1)=[O:9])=C>C(O)(C(F)(F)F)=O>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[C:11]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=2[F:36])=[C:12]2[CH:18]=[N:17][NH:16][C:13]2=[N:14][CH:15]=1)=[O:9]

Participants

3

Reactant 1

HCID 86656242HCID 86656242, compound

Product 1

HCID 446030814-(2-Fluoro-4-iodophenylamino)-1H-pyrazolo[3,4-b]pyridine 5-carboxylic acid (2-hydroxyethoxy)-amideYield 30%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
65 °C

Procedure

4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (2-vinyloxyethoxy)-amide (346 mg, 0.57 mmol) was dissolved in TFA (5 mL) and the reaction mixture heated at 65° C. for 3 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (10 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—SPE, gradient 0-10% methanol in DCM) to yield the title compound as a yellow solid (75 mg, 30%). LCMS (Method A): RT=6.67 min, [M+H]+=458. 1H NMR (DMSO-d6, 400 MHz) 13.51 (1H, s), 11.75 (1H, s), 10.38 (1H, s), 8.45 (1H, s), 7.80 (1H, dd, J=9.67, 1.86 Hz), 7.64-7.60 (1H, m), 7.30-7.21 (1H, m), 6.74 (1H, s), 4.71 (1H, s), 3.90 (2H, t, J=4.95 Hz), 3.61-3.56 (3H, m).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (10 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6fbdc15efc5348a0983adbdd13a8948c
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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