1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazine-1-carbonyl)-2-nitro-benzamide

HRID 571917Notes

Reaction equation

HRID 571917 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:15][C:16]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][C:19]=1[N+:27]([O-:29])=[O:28])=[O:17].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.[CH3:55][N:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:15][C:16](=[O:17])[C:18]1[CH:26]=[CH:25][C:21]([C:22]([N:59]2[CH2:60][CH2:61][N:56]([CH3:55])[CH2:57][CH2:58]2)=[O:24])=[CH:20][C:19]=1[N+:27]([O-:29])=[O:28]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 686709434-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-nitrobenzoic acid

Product 1

HCID 68671439N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazine-1-carbonyl)-2-nitro-benzamideYield 99.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-nitrobenzoic acid (500 mg, 1.11 mmol) in DMF (10 mL) was treated with 1-hydroxybenzotriazole (195 mg, 1.44 mmol), EDCI (276 mg, 1.44 mmol) and 1-methylpiperazine (0.16 mL, 1.44 mmol). The reaction was left at room temperature over night. The volatiles were removed by evaporation, the residue was added drop-wise to iced-water (25 mL) with stirring. A yellow solid was obtained which was extracted with DCM (2×25 mL). The combined organic layers were dried over sodium sulphate and evaporated leaving 590 mg of title compound which was employed in the following step without any further purification.

Workup

  1. waitThe reaction was left at room temperature over night
  2. customThe volatiles were removed by evaporation
  3. additionthe residue was added drop-wise to iced-water (25 mL)
  4. customA yellow solid was obtained which
  5. extractionwas extracted with DCM (2×25 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulphate
  7. customevaporated

Sources & evidence

ORD record
ord-a31479ee5af646208bc4d4130af2497c
Source dataset
uspto-grants-2015_05
Patent number
US09029356B2

Reaction notes

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