HCID 86656244, compound → HCID 44603142, compound

HRID 79057Notes

Reaction equation

HRID 79057 reaction equation
[OH:1][CH2:2][C:3]([CH3:36])([CH3:35])[O:4][NH:5][C:6]([C:8]1[C:9]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:10]2[CH:16]=[N:15][N:14](CC3C=CC(OC)=CC=3)[C:11]2=[N:12][CH:13]=1)=[O:7]>C(O)(C(F)(F)F)=O>[OH:1][CH2:2][C:3]([CH3:36])([CH3:35])[O:4][NH:5][C:6]([C:8]1[C:9]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:10]2[CH:16]=[N:15][NH:14][C:11]2=[N:12][CH:13]=1)=[O:7]

Participants

3

Reactant 1

HCID 86656244HCID 86656244, compound

Product 1

HCID 44603142HCID 44603142, compoundYield 11%

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-hydroxy-1,1-dimethylethoxy)-amide (420 mg, 0.69 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 resultant residue was dissolved in dichloromethane (10 mL) and methanol (2 mL) before being washed with aqueous saturated sodium bicarbonate solution (3×10 mL). The aqueous layer was extracted with dichloromethane (2×10 mL) and the combined organic extracts filtered through a hydrophobic frit then concentrated in vacuo. The resultant residue was purified by reverse-phase HPLC (gradient 10-95% methanol/water+0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm) to yield the title compound as a white solid (21 mg, 11%). LCMS (Method A): RT=7.71 min, [M+H]+=486. 1H NMR (DMSO-d6, 400 MHz) 13.53 (1H, s), 11.20 (1H, s), 10.15 (1H, s), 8.49 (1H, s), 7.80 (1H, d, J=9.68 Hz), 7.63 (1H, d, J=8.38 Hz), 7.25 (1H, t, J=8.38 Hz), 6.70 (1H, s), 4.65 (1H, s), 1.17 (6H, s).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe resultant residue was dissolved in dichloromethane (10 mL)
  3. washmethanol (2 mL) before being washed with aqueous saturated sodium bicarbonate solution (3×10 mL)
  4. extractionThe aqueous layer was extracted with dichloromethane (2×10 mL)
  5. filtrationthe combined organic extracts filtered through a hydrophobic frit
  6. concentrationthen concentrated in vacuo
  7. customThe resultant residue was purified by reverse-phase HPLC (gradient 10-95% methanol/water+0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm)

Sources & evidence

ORD record
ord-a55c45f5b7054b6bab6fa293cd18617c
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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