4-Bromoaniline → 1-[(4-bromo-phenylimino)-ethoxycarbonylamino-methyl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428841Notes

Reaction equation

HRID 1428841 reaction equation
[N:1]([C:4]([O:6][CH2:7][CH3:8])=[O:5])=[C:2]=S.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1.C(N(CC)CC)C.[NH:24]1[CH:28]=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:26]=[N:25]1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH2:32]([O:31][C:29]([C:27]1[CH:28]=[N:24][N:25]([C:2](=[N:16][C:13]2[CH:14]=[CH:15][C:10]([Br:9])=[CH:11][CH:12]=2)[NH:1][C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH:26]=1)=[O:30])[CH3:33]

Participants

7

Reactant 5

HCID 78074-BromoanilineHCID 8471TriethylamineHCID 85320Ethyl isothiocyanatoformateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 1363371681-[(4-bromo-phenylimino)-ethoxycarbonylamino-methyl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 40.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Ethyl isothiocyanatoformate (1.44 mL, 12.2 mmol) was added to a solution of 4-bromo-phenylamine (1.91 g, 11.1 mmol) and DCM (37 mL). After 1 h, triethylamine (4.65 mL, 33.4 mmol) was added to the reaction mixture, followed by ethyl pyrazole-4-carboxylate (1.87 g, 13.3 mmol), and EDCl (3.20 g, 16.7 mmol). After 18 h, the reaction mixture was diluted with DCM (150 mL), washed with brine (50 mL), dried (MgSO4), and concentrated. The residue was purified by FCC (5-40% EtOAc/hexanes) to yield the titled compound (1.84 g, 40% yield). MS (ESI/Cl): mass calcd. for C16H17BrN4O4, 408.1; m/z found, 409.1 [M+H]+.

Workup

  1. waitAfter 18 h
  2. washwashed with brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by FCC (5-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-dd9485f2e6b14e73b27df7e43ef3ca67
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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