1,2-Dichloroethane → 1-(6-bromo-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428842Notes

Reaction equation

HRID 1428842 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11](=[N:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=2)[NH:12][C:13](OCC)=[O:14])[CH:10]=1)=[O:5])[CH3:2].ClCCCl>[Ti](Cl)(Cl)(Cl)Cl.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[NH:12][C:13](=[O:14])[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Br:25])[CH:23]=3)[N:18]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 111,2-DichloroethaneHCID 1363371681-[(4-bromo-phenylimino)-ethoxycarbonylamino-methyl]-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 1363371691-(6-bromo-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl esterYield 64.2%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Titanium (IV) chloride (2.47 mL, 22.5 mmol) was carefully added to a solution of 1-[(4-bromo-phenylimino)-ethoxycarbonylamino-methyl]-1H-pyrazole-4-carboxylic acid ethyl ester (1.84 g, 4.50 mmol) and DCE (45 mL), and the resulting solution was heated to 100° C. for 15 h. The reaction mixture was cooled to room temperature and poured into ice water (50 mL) and DCM (100 mL) was added. The biphasic mixture was stirred for 2 h, and the layers were separated. The aqueous layer was further extracted with DCM (2×50 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4), and concentrated. The residue was triturated from EtOH to yield the titled compound (1.05 g, 64% yield). MS (ESI/Cl): mass calcd. for C14H11BrN4O3, 362.0; m/z found, 363.0 [M+H]+. 1H NMR (600 MHz, DMSO-d6): 13.15 (s, 1H), 9.01 (d, J=0.5 Hz, 1H), 8.33 (s, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.99 (dd, J=8.7, 2.4 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 4.30 (q, J=7.1 Hz, 2H), 1.32 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionwas added
  3. customthe layers were separated
  4. extractionThe aqueous layer was further extracted with DCM (2×50 mL)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was triturated from EtOH

Sources & evidence

ORD record
ord-05ac8d95af914ee7abd2b72217c5adc7
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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