Dimethylformamide → 1-((2H-tetrazol-5-yl)methyl)-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one

HRID 1183771Notes

Reaction equation

HRID 1183771 reaction equation
[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=3)[CH:8]=2)[N:3]1[CH2:22][C:23]#[N:24].[N:25]([Si](C)(C)C)=[N+:26]=[N-:27].C([Sn](=O)CCCC)CCC.CN(C)C=O>C(OCC)(=O)C.C(OCC)C>[N:24]1[NH:25][N:26]=[N:27][C:23]=1[CH2:22][N:3]1[C:4]2[C:9](=[CH:8][C:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:14][CH:13]=3)=[CH:6][CH:5]=2)[CH2:10][CH2:11][C:2]1=[O:1]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 61221Dibutyltin oxideHCID 78378Azidotrimethylsilane2×HCID 462023902-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetonitrile

Product 1

HCID 593166211-((2H-tetrazol-5-yl)methyl)-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-oneYield 80%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

A Biotage microwave vial was charged with 2-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetonitrile (66 mg, 0.20 mmol), azidotrimethylsilane (46 mg, 0.40 mmol), dibutyltin oxide (8 mg, 0.03 mmol), and anhydrous N,N-dimethylformamide (2.5 mL), and the vial capped. The reaction mixture was heated to 160° C. and irradiated for 25 minutes. LCMS showed only ca 63% conversion. Additional azidotrimethylsilane (46 mg, 0.40 mmol) was added, and heated again at 160° C. for an additional 30 minutes. LCMS showed the disappearance of starting material. The reaction mixture was diluted with ethyl acetate (30 mL), washed with 30% aqeuous ammonium chloride (2×10 mL), brine (20 mL), and dried over sodium sulfate. The solvent was removed from the solution under reduced pressure to give a pale yellow solid. Ethyl ether (3 mL) was added, sonicated, filtered, washed with ethyl ether (10 mL), dried to afford 1-((2H-tetrazol-5-yl)methyl)-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one as a white solid (59 mg, 0.16 mmol, 80%). LCMS mz 374.0 (M+H), anal HPLC>97% purity, 1HNMR (400 MHz, CD3CN) δ 7.83 (m, 4H); 7.65 (d, J=2.0 Hz, 1H); 7.62 (dd, J=8.4 and 2.1 Hz, 1H); 7.30 (d, J=8.6 Hz, 1H); 5.46 (s, 2H); 3.11 (m, 2H); 2.77 (m, 2H).

Workup

  1. customirradiated for 25 minutes
  2. temperatureheated again at 160° C. for an additional 30 minutes
  3. washwashed with 30% aqeuous ammonium chloride (2×10 mL), brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed from the solution under reduced pressure
  6. customto give a pale yellow solid
  7. customsonicated
  8. filtrationfiltered
  9. washwashed with ethyl ether (10 mL)
  10. customdried

Sources & evidence

ORD record
ord-8165cd0305024fd4aacebbbe9789a2a0
Source dataset
uspto-grants-2014_03
Patent number
US08664379B2

Reaction notes

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