2-Methoxyethanol → 6-Chloro-2-(2-methoxy-ethoxy)-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexyl methyl)-amide

HRID 1056672Notes

Reaction equation

HRID 1056672 reaction equation
[H-].[Na+].[CH3:3][O:4][CH2:5][CH2:6][OH:7].[F:8][C:9]1([F:31])[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]3[CH:21]=[CH:22][C:23](Cl)=[N:24][C:25]=3[CH:26]=[CH:27][C:28]=2[Cl:29])=[O:18])[CH2:11][CH2:10]1>C1COCC1>[F:8][C:9]1([F:31])[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]3[CH:21]=[CH:22][C:23]([O:7][CH2:6][CH2:5][O:4][CH3:3])=[N:24][C:25]=3[CH:26]=[CH:27][C:28]=2[Cl:29])=[O:18])[CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 1185559652,6-Dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide

Product 1

HCID 1185666066-Chloro-2-(2-methoxy-ethoxy)-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexyl methyl)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 60% NaH (38.28 mg, 2.0 eq) in THF (5.00 mL, 25.00 V) at 0° C. was added 2-methoxy-ethanol (54.74 mg, 0.72 mmol, 1.50 eq) and stirred for 30 min. Then 2,6-dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide (200 mg, 0.48 mmol, 1.00 eq) was added to reaction mixture at 0 OC and stirred at RT for 12 h. The reaction was quenched with ice water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and evaporated to dryness. The crude product was purified by column chromatography to afford. The title compound as (46 mg, 0.1 mmol, 22.3%) as a off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.74 (t, J=5.6 Hz, 1H), 7.73 (d, J=9.61 Hz, 1H), 7.49-7.55 (m, 2H), 7.17 (d, J=9.62 Hz, 1H), 3.23 (t, J=6.41 Hz, 2H), 3.15 (s, 6H), 1.99-2.05 (m, 2H), 1.75-1.85 (m, 5H), 1.22-1.28 (m, 2H). m/z: 413.0 [M+H]+

Workup

  1. stirringstirred at RT for 12 h
  2. customThe reaction was quenched with ice water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. customevaporated to dryness
  6. customThe crude product was purified by column chromatography
  7. customto afford

Sources & evidence

ORD record
ord-0377190519ec4d4799fe3229b7eb645e
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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