Tetrahydrofuran → HCID 53252017, compound

HRID 1619352Notes

Reaction equation

HRID 1619352 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:26])[N:15]4[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20][C:16]4=[N:17]3)=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:27]1COCC1>[CH3-].C[Al+]C.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Ti+3]>[F:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:26])[N:15]4[CH2:24][CH2:23][C:22](=[CH2:27])[CH2:21][CH2:20][C:16]4=[N:17]3)=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 58574177HCID 58574177, compound

Product 1

HCID 53252017HCID 53252017, compound

Reagents, catalysts & solvents 1

HCID 53384502mu-Chlorobis(eta5-cyclopentadienyl)(dimethylaluminum)-mu-methylenetitaniumCatalyst

Procedure

A solution of 3-((3-fluorophenyl)ethynyl)-6,7,9,10-tetrahydroazepino[2,1-b]-quinazoline-8,12-dione (0.1 g, 0.29 mmol, 1 equiv) and Tebbe Reagent in THF (5 mL) was stirred at rt for half an hour. Then the reaction mixture was quenched with NaOH aqueous and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to give the desired product, which was purified by silica gel chromatography. MS (ESI): 345 (M+H+); 1H NMR (300 MHz, CDCl3) δ 8.26-8.23 (d, J=8.19 Hz, 1H), 7.78 (s, 1H) 7.58-7.55 (dd, J=8.24, 1.52 Hz, 1H), 7.38-7.32 (m, 2H), 7.28-7.26 (m, 1H), 7.13-7.06 (m, 1H), 4.88-4.86 (d, J=7.50 Hz, 2H), 4.42-4.39 (m, 2H), 3.14-3.10 (m, 2H), 2.61-2.51 (m, 4H). mGluR5 PAM EC50: +++++. Fold shift at 10 μM: ++.

Workup

  1. customThen the reaction mixture was quenched with NaOH aqueous
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-03cced2e4df04514b69b24dd9fee2782
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

Loading…