Methyl iodide → HCID 16035851, compound

HRID 222304Notes

Reaction equation

HRID 222304 reaction equation
[OH:1][C@@H:2]([C:4]1[CH:5]=[CH:6][C:7]2[CH:23]=[CH:22][C:11]3=[N:12][CH:13]=[C:14]([C:16]4[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=4)[CH:15]=[C:10]3[C:9](=[O:24])[C:8]=2[CH:25]=1)[CH3:3].[H-].[Na+].[CH3:28]I.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:28][O:1][C@@H:2]([C:4]1[CH:5]=[CH:6][C:7]2[CH:23]=[CH:22][C:11]3=[N:12][CH:13]=[C:14]([C:16]4[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=4)[CH:15]=[C:10]3[C:9](=[O:24])[C:8]=2[CH:25]=1)[CH3:3]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 16035740HCID 16035740, compound

Product 1

HCID 16035851HCID 16035851, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

7-[(1R)-1-hydroxyethyl]-3-(1-methyl-1H-pyrazol-4-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (7 mg, 0.02 mmol) was dissolved in 1 mL of tetrahydrofuran. Sodium hydride (10 mg of 60% dispersion in oil) was added and the reaction was stirred at room temperature for 2 hours. Methyl iodide (26 μL, 0.42 mmol) was added and the reaction was stirred an additional 3 hours. The reaction was then poured into a mixture of ethyl acetate and saturated aqueous ammonium chloride. The aqueous layer was extracted twice with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, concentrated in vacuo, and purified via reverse phase HPLC (10-100% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier) to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 9.05 (d, 1H); 8.73 (s, 1H); 8.21 (d, 1H); 7.94 (s, 1H); 7.85 (s, 1H); 7.73 (dd, 1H); 7.65 (d, 1H); 7.51 (d, 1H); 7.34 (d, 1H); 4.47 (q, 1H); 4.01 (s, 3H); 3.27 (s, 3H); 1.46 (d, 3H). LRMS (APCI) calc'd for (C21H20N3O2) [M+H]+, 346.2; found 346.2.

Workup

  1. stirringthe reaction was stirred an additional 3 hours
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified via reverse phase HPLC (10-100% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier)

Sources & evidence

ORD record
ord-6d0c2efed08844bda09b3b78a1dec97b
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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