Styrene → HCID 58574509, compound

HRID 1619407Notes

Reaction equation

HRID 1619407 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:16])[N:7]3[CH2:14][CH:13]([CH3:15])[CH2:12][C:8]3=[N:9][C:10]=2[CH:11]=1.[CH2:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CCN(CC)CC>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][CH:13]1[CH2:14][N:7]2[C:8](=[N:9][C:10]3[CH:11]=[C:2](/[CH:17]=[CH:18]/[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:3]=[CH:4][C:5]=3[C:6]2=[O:16])[CH2:12]1

Participants

8

Reactant 3

HCID 7501StyreneHCID 8471TriethylamineHCID 58574490HCID 58574490, compound

Product 1

HCID 58574509HCID 58574509, compoundYield 61.6%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-bromo-2-methyl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (100 mg, 0.36 mmol), styrene (75 mg, 0.72 mmol), Pd (PPh3)4 (45 mg, 0.036 mmol), PPh3 (1 mg, 0.0036 mmol) and Et3N (182 mg, 1.8 mmol) in DMF (10 mL) was stirred at 140° C. under N2 for 8 hours. After cooled to room temperature, the mixture was diluted with H2O and extracted with EtOAc. The combined organic layer was washed with brine and dried over Na2SO4. Then the filtrate was concentrated and purified by column chromatography to give the desired product (67 mg). MS (ESI): 303 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 8.13-8.10 (d, J=8.3 Hz, 1H), 7.87-7.84 (d, J=8.4 Hz, 1H), 7.80 (s, 1H), 7.70-7.68 (d, J=7.5 Hz, 2H), 7.56-7.47 (m, 2H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 4.29-4.22 (dd, J=11.7, 7.8 Hz, 1H), 3.68-3.62 (dd, J=11.7, 6.8 Hz, 1H), 3.38-3.29 (dd, J=17.2, 8.1 Hz, 1H), 2.91-2.83 (dd, J=17.2, 7.5 Hz, 1H), 2.75-2.67 (m, 1H), 1.18-1.16 (d, J=6.7 Hz, 3H). mGluR5 PAM EC50: +++.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationThen the filtrate was concentrated
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-16b3b29b81d141b2a1d98a18b46c2d7a
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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