Dimethylformamide → 1-(6,7-dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428815Notes

Reaction equation

Cl[Si](C)(C)C.[CH2:6]([O:8][C:9]([C:11]1[CH:12]=[N:13][N:14]([C:16]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=2)=[N:17][C:18](OCC)=[O:19])[CH:15]=1)=[O:10])[CH3:7].CN(C=O)C>O>[CH2:6]([O:8][C:9]([C:11]1[CH:12]=[N:13][N:14]([C:16]2[NH:17][C:18](=[O:19])[C:29]3[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=2)[CH:15]=1)=[O:10])[CH3:7]

Participants

Conditions

Temperature: 80 °C

Procedure

Chlorotrimethylsilane (1.26 mL, 10.0 mmol) was added to a solution of 1-[(3,4-dimethoxy-phenylamino)-ethoxycarbonylimino-methyl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.39 g, 1.0 mmol) and DMF (3 mL), and the resulting mixture was heated to 80° C. for 16 h in a sealed tube. The reaction mixture was cooled and water (2 mL) was added. The crude reaction mixture was concentrated under reduced pressure and the resulting aqueous mixture was adjusted to pH 7 using 2M aqueous NH4OH. The residue was triturated well and collected by vacuum filtration. The titled compound was purified by preparative reverse-phase HPLC (0.28 g, 81%). MS (ESI): mass calcd. for C16H16N4O5, 344.4; m/z found, 345.7 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 13.06-12.23 (br m, 1H), 8.97 (s, 1H), 8.28 (s, 1H), 7.47 (s, 1H), 7.21 (s, 1H), 4.29 (q, J=7.1 Hz, 2H), 3.93 (s, 3H), 3.89 (s, 3H), 1.32 (t, J=7.1 Hz, 3H).

Workup

temperatureThe reaction mixture was cooled
customThe crude reaction mixture
concentrationwas concentrated under reduced pressure
customThe residue was triturated well
filtrationcollected by vacuum filtration
customThe titled compound was purified by preparative reverse-phase HPLC (0.28 g, 81%)

Sources & evidence

ORD record: ord-34de41733dfe49e68ec8ad8aa289056d
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08937078B2

Reaction notes

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