Dimethylformamide → HCID 58574762, compound

HRID 1619406Notes

Reaction equation

HRID 1619406 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:18])[N:7]3[CH2:16][CH2:15][CH:14]([CH3:17])[CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1.[CH2:19]=[CH:20][C:21]1C=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C[N:53](C=O)C>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:17][CH:14]1[CH2:15][CH2:16][N:7]2[C:8](=[N:9][C:10]3[C:5]([C:6]2=[O:18])=[CH:4][CH:3]=[C:2](/[CH:19]=[CH:20]/[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][N:53]=2)[CH:11]=3)[CH2:12][CH2:13]1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 7501StyreneHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 58574190HCID 58574190, compound

Product 1

HCID 58574762HCID 58574762, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Procedure

A solution of 3-bromo-8-methyl-7,8,9,10-tetrahydroazepino[2,1-b]quinazolin-12(6H)-one (100 mg, 0.42 mmol), styrene (100 mg, 0.33 mmol), Cs2CO3 (128 mg, 0.396 mmol), Bu4NBr (106 mg, 0.33 mmol), PPh3 (43.2 mg, 0.165 mmol) and Pd(OAc)2 (7.4 mg, 0.033 mmol) in DMF (10 mL) was stirred at 140° C. in a sealed tube for 8 hours. After it was cooled to room temperature, the mixture was diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. Then the filtration was concentrated and purified by column chromatography to give the desired product. MS (ESI): 332 (MH+); 1H NMR (300 MHz, CD3OD) δ 8.84-8.83 (d, J=5.73 Hz, 1H), 8.68-8.62 (m, 1H), 8.53-8.51 (d, J=8.22 Hz, 1H), 8.43-8.41 (d, J=8.37 Hz, 1H), 8.20-8.10 (m, 2H), 8.06 (s, 1H), 8.03-7.98 (t, J=13.57 Hz, 1H), 7.74-7.69 (d, J=16.47 Hz, 1H), 5.24-5.17 (dd, J=14.92, 6.84 Hz, 1H), 3.95-3.86 (m, 1H), 3.51-3.37 (m, 2H), 2.24-2.01 (m, 3H), 1.64-1.52 (m, 1H), 1.45-1.33 (m, 1H), 1.07-1.05 (d, J=6.45 Hz, 3H). mGluR5 PAM EC50: ++.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationThen the filtration
  5. concentrationwas concentrated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-1815bca7b64a4cdf8420777ecf8113c7
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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