Methyl iodide → HCID 69199678, compound

HRID 2376223Notes

Reaction equation

HRID 2376223 reaction equation
[CH2:1]([O:3][C:4](=[O:35])[CH:5]([C:28]1[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=1)[CH2:6][C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[N:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:8]=1)[CH3:2].[CH3:36][Si]([N-][Si](C)(C)C)(C)C.[Na+].IC>C1COCC1>[CH2:1]([O:3][C:4](=[O:35])[C:5]([CH3:36])([C:28]1[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=1)[CH2:6][C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[N:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 23568907HCID 23568907, compound

Product 1

HCID 69199678HCID 69199678, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid ethyl ester (Method 2, product from alkylation step before hydrolysis) (50 mg, 0.10 mmol) in THF (1.0 mL) at 0° C. was added a 1.0 M solution of NaHMDS (0.15 mL, 0.15 mmol). The solution was stirred at 0° C. for 2 h, then iodomethane (41 mg, 0.29 mmol) was added neat. After stirring for 1 h the reaction was quenched with saturated ammonium chloride (50 mL), and the reaction mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (1×50 mL) and dried with Na2SO4, and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography (EtOAc/hexanes) giving 31 mg (60%) of 3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-methyl-2-m-tolyl-propionic acid ethyl ester. HPLC: Rt=3.79 (Method B). MS (ES+): mass calculated for C29H28Cl2N2O3, 522.15; m/z found 523.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 7.58 (d, J=8.4 Hz, 1H), 7.42 (d, J=2.0 Hz, 1H), 7.25 (t, J=7.6 Hz, 1H), 77.17-7.14 (m, 4H), 7.08 (d, J=7.4 Hz, 1H), 7.05 (dd, J=2.0 Hz, 8.3 Hz, 1H), 6.97 (d, J=8.9 Hz, 2H), 6.22 (s, 1H), 4.10 (m, 2H), 3.77 (s, 3H), 3.40 (d, J=13.9 Hz, 1H), 3.17 (d, J=13.9 Hz, 1H), 2.13 (s, 3H), 1.49 (s, 3H), 1.12 (t, J=7.1 Hz, 3H).

Workup

  1. stirringAfter stirring for 1 h the reaction
  2. customwas quenched with saturated ammonium chloride (50 mL)
  3. extractionthe reaction mixture was extracted with EtOAc (3×50 mL)
  4. washThe combined organic layers were washed with brine (1×50 mL)
  5. dry with materialdried with Na2SO4
  6. customthe solvent was removed under reduced pressure
  7. customThe crude material was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-83a46eeb3e094c6eb93a56e557de3c77
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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