1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(2-Fluoro-4-iodo-phenylamino)-1H-indazole-5-carboxylic acid methoxy-methyl-amide

HRID 79070Notes

Reaction equation

HRID 79070 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]CN=C=NCCCN(C)C.C1C=C[C:36]2[N:41]([OH:42])N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:22][O:42][N:41]([CH3:36])[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

7

Reactant 4

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

Product 1

HCID 446032064-(2-Fluoro-4-iodo-phenylamino)-1H-indazole-5-carboxylic acid methoxy-methyl-amideYield 45.2%

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 N—O-dimethyl-hydroxylamine (21 mg, 0.21 mmol) in DMF (3 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 then azeotroped with diethyl ether to give a pale tan foam (35 mg, 45%). LCMS (Method A): RT=9.63 min, [M+H]+=441. 1H NMR (DMSO-d6, 400 MHz) 13.16 (1 H, s), 8.25 (1 H, s), 7.59-7.51 (2 H, m), 7.34-7.28 (2 H, m), 7.14 (1 H, d, J=8.55 Hz), 6.71 (1 H, t, J=8.73 Hz), 3.38 (3 H, s), 3.10 (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. customthen azeotroped with diethyl ether

Sources & evidence

ORD record
ord-520dce36e7bb4803a63c58547f1366a0
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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