Trifluoroacetic acid → 3-(4-methoxybenzyl)-9-(methylsulfanyl)-6,7-dihydro-3H-pyrazolo[4',3':5,6]pyrido[4,3-f]quinazoline

HRID 2383407Notes

Reaction equation

C[N:2](/[CH:4]=[C:5]1/[C:6](=O)[C:7]2[CH:8]=[N:9][C:10]([S:15][CH3:16])=[N:11][C:12]=2[CH2:13][CH2:14]/1)[CH3:3].[CH3:18][O:19][C:20]1[CH:32]=[CH:31][C:23]([CH2:24][N:25]2C(N)=[CH:28][CH:27]=[N:26]2)=[CH:22][CH:21]=1.FC(F)(F)C(O)=O>CO.C(O)(C)C>[CH3:18][O:19][C:20]1[CH:32]=[CH:31][C:23]([CH2:24][N:25]2[C:3]3[N:2]=[CH:4][C:5]4[CH2:14][CH2:13][C:12]5[N:11]=[C:10]([S:15][CH3:16])[N:9]=[CH:8][C:7]=5[C:6]=4[C:28]=3[CH:27]=[N:26]2)=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of (E)-6-((dimethylamino)methylene)-2-(methylthio)-7,8-dihydroquinazolin-5(6H)-one (8 g, 32 mmol) and 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (7.2 g, 35 mmol) was added trifluoroacetic acid (3 mL). The reaction mixture was heated at 100° C. for 16 hours. The reaction was cooled to room temperature and diluted with a 1:1 mixture of methanol and isopropanol (40 mL). The mixture was stirred for 30 minutes and filtered. The solid obtained was then further purified using flash column chromatography (SiO2, gradient from 100% chloroform to 2% EtOAc in chloroform) to give the desired product (3.0 g, 24%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 9.52 (s, 1H), 7.98 (s, 1H), 7.82 (s, 1H), 7.40 (d, J=8.0 Hz, 2H), 6.82 (d, J=8.0 Hz, 2H), 5.64 (s, 2H), 3.78 (s, 3H), 3.16 (t, J=6.0 Hz, 2H), 3.10 (t, J=6.2 Hz, 2H), 2.65 (s, 3H); LCMS [M+H]: 390.

Workup

temperatureThe reaction was cooled to room temperature
filtrationfiltered
customThe solid obtained
customwas then further purified

Sources & evidence

ORD record: ord-05dc7c4f22ba420ca333ca691a390dc6
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08263610B2

Reaction notes

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