Dimethylformamide → HCID 51001018, compound

HRID 82463Notes

Reaction equation

HRID 82463 reaction equation
[OH:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1.Cl[C:32]([F:37])([F:36])C([O-])=O.[Na+].CN(C=O)C>C(#N)C.C(OCC)(=O)C>[F:36][CH:32]([F:37])[O:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 2734985Sodium chlorodifluoroacetateHCID 178514923HCID 178514923, compound

Product 1

HCID 51001018HCID 51001018, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-[(6-hydroxypyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 29, 0.025 g, 0.062 mmol) in 1 mL of acetonitrile was added sodium chlorodifluoroacetate (0.010 g, 0.068 mmol). The reaction was heated to reflux under an atmosphere of nitrogen for 4 h, and then DMF (0.310 mL) was added. The mixture was heated to 100° C. for 1 h, cooled to rt, and diluted with ethyl acetate. The organic solution was washed 3× with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 454.1573 for [M+H]+ [Calc'd for C24H22F2N3O4, [M+H]+=454.1573]: 1H NMR (400 MHz, CDCl6) S 8.90-8.88 (m, 1H), 8.26 (s, 1H), 8.03 (s, 1H), 7.77-7.75 (m, 2H), 7.65-7.59 (m, 2H), 7.43-7.40 (m, 1H), 7.37 (t, J=73.2 Hz, 1H), 6.73 (d, J=8.4 Hz, 1H), 4.84-4.77 (m, 1H), 4.25 (s, 2H), 4.22-4.06 (m, 3H), 3.59-3.53 (m, 1H), 3.45 (br s, 1H), 3.35-3.30 (m, 1H), 2.21-1.96 (m, 1H), 2.00-1.96 (m, 1H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux under an atmosphere of nitrogen for 4 h
  3. temperaturecooled to rt
  4. washThe organic solution was washed 3× with water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel chromatography
  9. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-815f642839e84b32a5ca16bd6c91837b
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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