Triethylamine → HCID 58574283, compound

HRID 1619409Notes

Reaction equation

HRID 1619409 reaction equation
[CH3:1][C:2]1([CH3:19])[CH2:15][CH2:14][N:13]2[C:4](=[N:5][C:6]3[C:11]([C:12]2=[O:16])=[CH:10][CH:9]=[C:8]([CH:17]=[CH2:18])[CH:7]=3)[CH2:3]1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CN1C(=O)CCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1/[CH:18]=[CH:17]/[C:8]1[CH:7]=[C:6]2[C:11]([C:12](=[O:16])[N:13]3[CH2:14][CH2:15][C:2]([CH3:19])([CH3:1])[CH2:3][C:4]3=[N:5]2)=[CH:10][CH:9]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 612591-Bromo-2-fluorobenzeneHCID 58574574HCID 58574574, compound

Product 1

HCID 58574283HCID 58574283, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 167845palladium(II) acetateCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 7,7-dimethyl-3-vinyl-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one (116 mg, 0.4 mmol, 1 equiv), 1-bromo-2-fluorobenzene (140 mg, 0.8 mmol, 2 equiv), Cs2CO3 (260 mg, 0.8 mmol, 2 equiv), Pd(OAc)2 (576 mg, 0.08 mmol, 0.2 equiv), Ph3P (88 mg, 0.32 mmol, 0.8 equiv), Et3N (80 mg, 0.8 mmol, 2 equiv) and (n-Bu)4NI (256 mg, 0.8 mmol, 2 equiv) in NMP was stirred at 140° C. for 20 minutes in a microwave reactor. After that, the reaction mixture was cooled to rt. The reaction was quenched with water (20 mL) and extracted with ethyl acetate (3×20 mL). The organic combined organic layers were dried over Na2SO4 and concentrated. The crude was purified by silica gel chromatography to produce 53 mg desired product. MS (ESI): 349 (MH+); 1H NMR (300 MHz, CD3OD) δ 8.20-8.17 (d, J=8.12 Hz, 1H), 7.80-7.68 (m, 2H), 7.56 (s, 1H), 7.43-7.19 (m, 3H), 7.15-6.99 (m, 2H), 4.12-3.92 (t, J=13.20 Hz, 2H), 2.82 (s, 2H), 1.85-1.72 (t, J=12.84 Hz, 2H), 1.15 (s, 6H). mGluR5 PAM EC50: +++.

Workup

  1. customThe reaction was quenched with water (20 mL)
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe organic combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude was purified by silica gel chromatography

Sources & evidence

ORD record
ord-2bfcde8bd8ad42f4ad9dc0f895dc4a56
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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