Triethylamine → HCID 53252015, compound

HRID 1619401Notes

Reaction equation

HRID 1619401 reaction equation
Br[C:2]1[CH:17]=[CH:16][N:5]2[C:6](=[O:15])[C:7]3[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:8]=3[N:9]=[C:4]2[CH:3]=1.[C:18]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)#[CH:19].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:18]#[C:19][C:2]2[CH:17]=[CH:16][N:5]3[C:6](=[O:15])[C:7]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:8]=4[N:9]=[C:4]3[CH:3]=2)=[CH:21][CH:22]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 5226271-Ethynyl-4-fluorobenzeneHCID 58574318HCID 58574318, compound

Product 1

HCID 53252015HCID 53252015, compoundYield 65.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-bromo-7,8,9,10-tetrahydrocyclohepta[d]pyrido[1,2-a]pyrimidin-11(6H)-one (250 mg, 0.85 mmol), 1-ethynyl-4-fluorobenzene (255 mg, 2.12 mmol), Pd(OAc)2 (38.2 mg, 0.17 mmol), PPh3 (200 mg, 0.76 mmol), CuI (16.2 mg, 0.085 mmol), and Et3N (0.7 mL) in DMF (8 mL) was stirred in a sealed tube at 70° C. for 3.5 hours. After it was cooled to room temperature, the reaction mixture was diluted with H2O and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration, the crude product was purified by silica gel to produce 185 mg of desired product. MS (ESI): 333 (MH+); 1H NMR (300 MHz, CDCl3) δ 8.97-8.94 (dd, J=7.44, 0.66 Hz, 1H), 7.65-7.56 (m, 3H), 7.15-7.06 (m, 3H), 3.00-2.97 (m, 4H), 1.94-1.88 (m, 2H), 1.80-1.64 (m, 4H). mGluR5 PAM EC50: +++++. Fold shift at 10 μM: +.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration and concentration
  5. customthe crude product was purified by silica gel

Sources & evidence

ORD record
ord-f281f0d4e4c24f339bfa7bc9600437f1
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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