Styrene → HCID 53250274, compound

HRID 1619405Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:17])[N:7]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH2:43]=[CH:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:43](/[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:17])[N:7]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1)=[CH:44]\[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-bromo-7,8,9,10-tetrahydroazepino[2,1-b]quinazolin-12(6H)-one (100 mg, 0.34 mmol), Cs2CO3 (132.6 mg, 0.85 mmol), Pd(OAc)2 (30.6 mg, 0.14 mmol), PPh3 (103 mg, 0.34 mmol), Bu4NBr (109.5 mg, 0.34 mmol), and styrene (88.7 mg, 0.85 mmol) in DMF (6 mL) in a sealed tube was stirred at 120° C. for two hours. After it was cooled to room temperature, the reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over Na2SO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the desired product. MS (ESI): 317 (MH+); 1H NMR (300 MHz, CDCl3) δ 8.08-8.05 (d, J=8.19 Hz, 1H), 7.78-7.74 (m, 2H), 7.68-7.66 (m, 2H), 7.54-7.30 (m, 5H), 4.34-4.31 (m, 2H), 3.05 (broad, 2H), 1.73-1.70 (m, 6H). mGluR5 PAM EC50: +++++. Fold shift at 10 μM: ++.

Workup

temperatureAfter it was cooled to room temperature
customthe reaction mixture was quenched with water (20 mL)
extractionextracted with ethyl acetate (3×20 mL)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationAfter filtration and concentration
customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-706ae3d6d54141b3a51b19d2cafab396
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772301B2

Reaction notes

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