O-Methylhydroxylamine → 4-[(2-Fluoro-4-iodophenyl)amino]-N-methoxy-1H-indazole-5-carboxamide

HRID 79069Notes

Reaction equation

HRID 79069 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[N:13][NH:14]2.[CH3:22][O:23][NH2:24].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:22][O:23][NH:24][C:19]([C:18]1[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:21]

Participants

8

Reactant 5

HCID 4113O-MethylhydroxylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 575215054-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid

Product 1

HCID 446032054-[(2-Fluoro-4-iodophenyl)amino]-N-methoxy-1H-indazole-5-carboxamideYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (70 mg, 0.176 mmol) and O-methyl-hydroxylamine (19 mg, 0.21 mmol) in DMF (2 mL) was added EDCI (40 mg, 0.21 mmol), HOBt (28 mg, 0.21 mmol) and DIPEA (70 μL, 0.42 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate then water, dried (Na2SO4), filtered and concentrated in vacuo. The resultant solid was triturated with a solution of hot methanol/water/NaHCO3, the solid filtered off, washed with water to give the title compound as a pale pink solid (33 mg, 44%). LCMS (Method A): RT=9.09 min, [M+H]+=427. 1H NMR (DMSO-d6, 400 MHz) 13.20 (1 H, s), 11.62 (1 H, s), 9.99 (1 H, s), 7.66 (1 H, dd, J=10.33, 1.94 Hz), 7.46-7.40 (2 H, m), 7.23 (1 H, s), 7.01 (1 H, d, J=8.78 Hz), 6.92 (1 H, t, J=8.66 Hz), 3.64 (3 H, s).

Workup

  1. washwashed with saturated aqueous sodium hydrogen carbonate
  2. dry with materialwater, dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resultant solid was triturated with a solution of hot methanol/water/NaHCO3
  6. filtrationthe solid filtered off
  7. washwashed with water

Sources & evidence

ORD record
ord-f371fd37be0342e98c8ba8a0aa0d9053
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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