1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-amino-5-bromo-2-(4-fluorophenyl)-N-methyl-2H-indazole-3-carboxamide

HRID 595703Notes

Reaction equation

HRID 595703 reaction equation
[NH2:1][C:2]1[C:3]([Br:21])=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[C:6]=2[C:18](O)=[O:19].C[CH2:23][N:24]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN.Cl>CN(C=O)C.CCN(CC)CC>[NH2:1][C:2]1[C:3]([Br:21])=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[C:6]=2[C:18]([NH:24][CH3:23])=[O:19]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6364545Methylamine hydrochlorideHCID 903325166-amino-5-bromo-2-(4-fluorophenyl)-2H-indazole-3-carboxylic acid

Product 1

HCID 903324916-amino-5-bromo-2-(4-fluorophenyl)-N-methyl-2H-indazole-3-carboxamideYield 78.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 6-amino-5-bromo-2-(4-fluorophenyl)-2H-indazole-3-carboxylic acid (1.0 g, 2.8 mmol) in dry DMF (500 mL) were added EDCI (1.1 g, 6.2 mmol) and HOBT (0.5 g, 4.3 mmol). The reaction mixture was stirred at room temperature for 1 h, and then Et3N (5 mL) and MeNH2.HCl (0.9 g, 14.3 mmol) were added to the reaction mixture. After stirring for another 2 hours, the reaction mixture was concentrated in vacuum and 300 mL Na2CO3 (a.q.) was added to the mixture. The resulting solid was filtered to give the crude product, which was purified by column chromatography (PE:EA=3:1) to give 6-amino-5-bromo-2-(4-fluorophenyl)-N-methyl-2H-indazole-3-carboxamide (0.8 g, yield: 74%). 1H-NMR (CDCl3, 400 MHz) δ 8.10 (s, 1H), 7.55˜7.58 (m, 2H), 7.20˜7.26 (m, 2H), 6.98 (s, 1H), 5.75 (s, 1H), 4.32 (s, 2H), 2.98 (d, J=4.8 Hz, 3H). MS (M+H)+: 363/365.

Workup

  1. stirringAfter stirring for another 2 hours
  2. concentrationthe reaction mixture was concentrated in vacuum and 300 mL Na2CO3 (a.q.)
  3. additionwas added to the mixture
  4. filtrationThe resulting solid was filtered
  5. customto give the crude product, which
  6. customwas purified by column chromatography (PE:EA=3:1)

Sources & evidence

ORD record
ord-fe3690130d6448d7b1c0f1070322c0c3
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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