1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-Ethoxy-4-[(2-fluoro-4-iodophenyl)amino]-1H-indazole-5-carboxamide

HRID 79066Notes

Reaction equation

HRID 79066 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](O)=[O:20])=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[N:13][NH:14]2.Cl.[CH2:23]([O:25][NH2:26])[CH3:24].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH2:23]([O:25][NH:26][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:20])[CH3:24]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 757711-Hydroxybenzotriazole2×HCID 76850O-ethylhydroxylamine hydrochloride2×HCID 81531Diisopropylethylamine2×HCID 575215054-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid

Product 1

HCID 44603148N-Ethoxy-4-[(2-fluoro-4-iodophenyl)amino]-1H-indazole-5-carboxamideYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (100 mg, 0.252 mmol) in DMF (3 mL) was added O-ethyl hydroxylamine hydrochloride (37 mg, 0.378 mmol), HOBt (37 mg, 0.277 mmol) and EDCI (53 mg, 0.277 mmol). The reaction mixture was stirred at room temperature for 1 hour then DIPEA (91 μl, 0.529 mmol) was added and the reaction stirred at room temperature for 18 hours. Additional quantities, as at the start of the reaction, of O-ethyl hydroxylamine hydrochloride, HOBt, EDCI and DIPEA were added to the reaction and stirring was continued for 4 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate, the solid precipitate in the mixture was filtered off, washed with water to give the title compound (41 mg, 37%). LCMS (Method A): RT=9.65 min, [M+H]+=441. 1H NMR (DMSO-d6, 400 MHz): 13.19 (1 H, s), 11.51 (1 H, s), 9.97 (1 H, s), 7.66 (1 H, dd, J=10.35, 1.95 Hz), 7.46 (1 H, d, J=8.78 Hz), 7.42 (1 H, dd, J=8.47, 1.84 Hz), 7.25 (1 H, s), 7.02 (1 H, d, J=8.76 Hz), 6.91 (1 H, t, J=8.66 Hz), 3.86 (2 H, q, J=7.04 Hz), 1.15 (3 H, t, J=7.03 Hz).

Workup

  1. stirringthe reaction stirred at room temperature for 18 hours
  2. customAdditional quantities, as at the start of the reaction
  3. stirringstirring
  4. waitwas continued for 4 hours
  5. washwashed with saturated aqueous sodium hydrogen carbonate
  6. filtrationthe solid precipitate in the mixture was filtered off
  7. washwashed with water

Sources & evidence

ORD record
ord-1b725d18b5b64a97ad9302a329014e3c
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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