Tetrahydrofuran → HCID 53252507, compound

HRID 1619312Notes

Reaction equation

HRID 1619312 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:25])[N:15]4[CH2:23][CH:22]([OH:24])[CH2:21][CH2:20][C:16]4=[N:17]3)=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH2:28]1COCC1>>[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:25])[N:15]4[CH2:23][CH:22]([O:24][CH3:28])[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 3

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 58574398HCID 58574398, compound

Product 1

HCID 53252507HCID 53252507, compound

Procedure

To a solution of 3-((3-fluorophenyl)ethynyl)-8-hydroxy-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one (0.2 g, 0.6 mmol, 1 equiv) in THF (15 mL) was added NaH (57.6 mg, 2.4 mmol, 4 equiv) in portions. After stirring at rt for 1 h, the reaction mixture was quenched with water and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over Na2SO4. After filtration and concentration, the residue was purified using silica gel chromatography to give the desired product. MS (ESI): 349 (M+H+); 1H NMR (300 MHz, CDCl3) δ 8.27-8.24 (d, J=8.46 Hz, 1H), 8.01 (s, 1H), 7.62-7.50 (d, J=8.19 Hz, 1H), 7.37-7.35 (m, 2H), 7.30-7.28 (m, 1H), 7.14-7.09 (m, 1H), 4.58-4.57 (m, 1H), 4.02-4.00 (m, 1H), 3.87-3.81 (m, 1H), 3.42 (s, 3H), 3.33-3.20 (m, 2H), 2.26-2.15 (m, 2H). mGluR5 PAM EC50: +++++. Fold shift at 10 μM: +.

Workup

  1. customthe reaction mixture was quenched with water
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified

Sources & evidence

ORD record
ord-ecc2dcc7b6d845dd859b79a75d692d53
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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