Trimethylphosphine → 4-[(5-chloropyridin-2-yl)methoxy]-1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one

HRID 1497376Notes

Reaction equation

HRID 1497376 reaction equation
[CH:1]1([N:4]2[C:12]([CH3:13])=[C:11]3[C:6]([CH:7]=[CH:8][C:9]([N:14]4[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]4=[O:21])=[CH:10]3)=[N:5]2)[CH2:3][CH2:2]1.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29]O)=[N:27][CH:28]=1.CP(C)C>O1CCCC1.C(OCC)(=O)C>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29][O:20][C:17]2[CH:18]=[CH:19][N:14]([C:9]3[CH:8]=[CH:7][C:6]4[C:11](=[C:12]([CH3:13])[N:4]([CH:1]5[CH2:2][CH2:3]5)[N:5]=4)[CH:10]=3)[C:15](=[O:21])[CH:16]=2)=[N:27][CH:28]=1

Participants

6

Reactant 3

HCID 68983TrimethylphosphineHCID 20537893(5-Chloropyridin-2-yl)methanolHCID 1177986831-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 1177986844-[(5-chloropyridin-2-yl)methoxy]-1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-oneYield 50.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one (30 mg) in tetrahydrofuran (2 ml) were added (5-chloropyridin-2-yl)methanol (31 mg), bis(2-methoxyethyl)azodicarboxylate (55 mg) and trimethylphosphine (1 M tetrahydrofuran solution, 235 μl) at room temperature, and the mixture was stirred at the same temperature for 2 hr. The mixture was diluted with ethyl acetate, and washed with water, 1 M aqueous sodium hydroxide solution and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) and recrystallized from ethyl acetate to give the title compound (22 mg).

Workup

  1. washwashed with water, 1 M aqueous sodium hydroxide solution and saturated brine
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)
  5. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-99b655fc09664f808d82ec396d039ce6
Source dataset
uspto-grants-2015_12
Patent number
US09199963B2

Reaction notes

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