HCID 53252176, compound → HCID 58574493, compound

HRID 1619410Notes

Reaction equation

HRID 1619410 reaction equation
[C:1]1([C:7]#[C:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13](=[O:24])[N:14]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][C:15]4=[N:16]3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(Cl)(Cl)Cl.CO.[OH-].[OH-].[Pd+2]>[CH2:8]([C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:24])[N:14]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][C:15]3=[N:16]2)=[CH:11][CH:10]=1)[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 1

HCID 53252176HCID 53252176, compound

Product 1

HCID 58574493HCID 58574493, compoundYield 39.3%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A solution of 3-(phenylethynyl)-7,8,9,10-tetrahydroazepino[2,1-b]-quinazolin-12(6H)-one (50 mg, 0.16 mmol) and Pd(OH)2/C in CHCl3 (10 mL) and MeOH (10 mL) was stirred under H2 (1 atm) at room temperature for 8 h. The reaction mixture was filtered and the filter cake was washed with water. The combined filtrate was extracted with ethyl acetate (3×20 mL) and dried over Na2SO4. After filtration and concentration, the residue was purified by preparative HPLC to give 20 mg of the desired product. MS (ESI): 319 (MH+); 1H NMR (300 MHz, CDCl3) δ 7.99-7.97 (d, J=8.10 Hz, 1H), 7.40 (s, 1H), 7.38-7.33 (d, J=8.22 Hz, 1H), 7.29-7.17 (m, 5H), 4.32-4.29 (t, J=4.98 Hz, 2H), 3.06-2.91 (m, 6H), 1.75 (broad, 4H), 1.68 (broad, 2H). mGluR5 PAM EC50: ++.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe filter cake was washed with water
  3. extractionThe combined filtrate was extracted with ethyl acetate (3×20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-5ab3b6cc75c34c68bfc2de4301442848
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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