Sodium hydride → US10023592, Example 245

HRID 575719Notes

Reaction equation

HRID 575719 reaction equation
[H-].[Na+].[CH:3]1([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:9]=2[C:18]2[CH:19]=[C:20]([CH3:25])[C:21](=[O:24])[NH:22][CH:23]=2)[CH2:5][CH2:4]1.CS(O[CH2:31][CH:32]1[CH2:35][O:34][CH2:33]1)(=O)=O>CN(C=O)C>[CH:3]1([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:9]=2[C:18]2[CH:19]=[C:20]([CH3:25])[C:21](=[O:24])[N:22]([CH2:31][CH:32]3[CH2:35][O:34][CH2:33]3)[CH:23]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86680078Oxetan-3-ylmethyl methanesulfonateHCID 1180216505-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-3-methyl-1H-pyridin-2-one

Product 1

HCID 118022437US10023592, Example 245Yield 24.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (42 mg, 1.04 mmol, 60% in mineral oil) was added to the title compound from Example 242, step 1 (80 mg) in anhydrous DMF (4 mL) After stirring 1 h, oxetan-3-ylmethyl methanesulfonate (173 mg, 1.04 mmol) was added and stirring continued for 18 h. EA extractive work up from 1 M HCl and preparative HPLC purification gave the title compound (24.0 mg) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 7.85 (d, J=8.8 Hz, 1H), 7.82 (s, 1H), 7.62 (s, 1H), 7.51 (s, 1H), 7.03 (d, J=8.8 Hz, 1H), 4.83 (t, J=7.2 Hz, 1H), 4.57 (t, J=6.4 Hz, 1H), 4.30 (d, J=7.2 Hz, 1H), 3.95 (d, J=6.8 Hz, 1H), 3.62-3.56 (m, 1H), 3.07 (s, 3H), 2.21 (s, 3H), 1.32-1.27 (m, 1H), 0.72-0.68 (m, 2H), 0.40-0.36 (m, 2H). LCMS: 404.1 (M+1)+

Workup

  1. stirringstirring
  2. waitcontinued for 18 h
  3. customEA extractive work up from 1 M HCl and preparative HPLC purification

Sources & evidence

ORD record
ord-1aef94eed57e434cba32f255895ccd91
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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