Ammonium Chloride → HCID 71565736, compound

HRID 922762Notes

Reaction equation

HRID 922762 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH2:18][N:19]4[N:23]=[N:22][C:21]([C:24]([OH:31])([CH2:29][CH3:30])[C:25]([F:28])([F:27])[F:26])=[N:20]4)=[CH:15][CH:16]=3)[N:11]=[C:10]([C:32]#[N:33])[CH:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=[O:35].C([O-])([O-])=O.OO.OO.OO.[Na+].[Na+].[Na+].[Na+].[NH4+].[Cl-]>CC(C)=O.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH2:18][N:19]4[N:23]=[N:22][C:21]([C:24]([OH:31])([CH2:29][CH3:30])[C:25]([F:28])([F:27])[F:26])=[N:20]4)=[CH:15][CH:16]=3)[N:11]=[C:10]([C:32]([NH2:33])=[O:35])[CH:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 159762Sodium percarbonateHCID 89544026HCID 89544026, compound

Product 1

HCID 71565736HCID 71565736, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

4-(4-Fluorophenyl)-7-{[5-(1,1,1-trifluoro-2-hydroxybutan-2-yl)-2H-tetrazol-2-yl]methyl}quinoline-2-carbonitrile (3-4, 14 mg, 0.031 mmol, 1.0 equiv) was dissolved in acetone (0.5 mL)/water (0.25 mL) and sodium percarbonate (48 mg, 0.15 mmol, 5.0 equiv) was added. The resulting mixture was heated to 50° C. for two hours. The mixture was cooled and poured over aqueous NH4Cl (1 mL), extracted with ethyl acetate (3×5 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash column chromatography (SiO2, 12 g ISCO column, 0-100% EtOAc/hexanes) to give 4-(4-fluorophenyl)-7-{[5-(1,1,1-trifluoro-2-hydroxybutan-2-yl)-2H-tetrazol-2-yl]methyl}quinoline-2-carboxamide (3-6) as a white solid. 1H NMR (3-6) (500 MHz, CDCl3): δ 8.28 (s, 1H); 8.17 (s, 1H); 8.06 (s, 1H); 7.99 (d, J=8.7 Hz, 1H); 7.55-7.44 (m, 3H); 6.05 (s, 2H); 5.84 (s, 1H); 3.92 (s, 1H); 2.33 (dt, J=14.4, 7.4 Hz, 1H); 2.20 (dt, J=14.3, 7.2 Hz, 1H); 0.84 (t, J=7.4 Hz, 3H). LRMS m/z (M+H) 474.9 found, 475.1 required. 1H NMR (3-7) (500 MHz, CD3OD): δ 8.12 (s, 1H); 8.08 (s, 1H); 7.96 (d, J=8.8 Hz, 1H); 7.64-7.55 (m, 3H); 7.34-7.29 (m, 2H); 6.25 (d, J=15.1 Hz, 1H); 6.15 (d, J=15.1 Hz, 1H); 2.57 (dd, J=14.4, 7.3 Hz, 1H); 2.13 (dq, J=14.4, 7.2 Hz, 1H); 0.78 (t, J=7.4 Hz, 3H). LRMS m/z (M+H)+ 474.7 found, 475.1 required.

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled
  3. extractionextracted with ethyl acetate (3×5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography (SiO2, 12 g ISCO column, 0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6ed68c71242148ee82aa943fabf3a1d6
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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