Sodium Hydroxide → [6-Methoxy-3-pyridinyl]methylamino-N-[4-(1-propynyl)-3-(trifluoromethyl)phenyl]benzamide

HRID 1830994

Reaction equation

HRID 1830994 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][NH:10][C:11]2[CH:30]=[CH:29][CH:28]=[CH:27][C:12]=2[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19](Br)=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=2)=[O:14])=[CH:5][CH:4]=1.[CH2:31]([Sn](CCCC)(CCCC)C#CC)[CH2:32][CH2:33]C.[OH-].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][NH:10][C:11]2[CH:30]=[CH:29][CH:28]=[CH:27][C:12]=2[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:31]#[C:32][CH3:33])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=2)=[O:14])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 2733165Tributyl(prop-1-yn-1-yl)stannaneHCID 99130292-[[6-Methoxy-3-pyridinyl]methyl]amino-N-[4-bromo-3-(trifluoromethyl)phenyl]benzamide

Product 1

HCID 9980607[6-Methoxy-3-pyridinyl]methylamino-N-[4-(1-propynyl)-3-(trifluoromethyl)phenyl]benzamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred solution of 2-[[6-methoxy-3-pyridinyl]methyl]amino-N-[4-bromo-3-(trifluoromethyl)-phenyl]-benzamide (Example 1; 3.98 g, 8.3 mmol) in dry toluene (200 mL) is purged with argon for 20 minutes at 25° C. Tributyl-1-propynylstannane (4.1 g of 80%, 9.96 mmol) and tetrakis(triphenylphosphine)palladium (0) (260 mg) are then added and the resulting mixture is heated at 100° C. for 17 hours under an argon atmosphere. The mixture is then cooled, treated with an aqueous solution of sodium hydroxide (85 mL of 0.1 M) and purged with air for 2 hours. The resulting mixture is extracted with EtOAc (3×100 mL). The organic phase is sequentially washed with water (2×40 mL) and saturated aqueous sodium chloride (1×40 mL), dried (Na2SO4), filtered and the solvent is evaporated under reduced pressure to yield the crude product which is purified by column chromatography on silica gel, eluent 33% EtOAc in hexane and recrystallised from diethylether-hexane to give the title compound as a pale-yellow crystalline solid; m.p. 123–124° C.

Workup

  1. temperatureThe mixture is then cooled
  2. custompurged with air for 2 hours
  3. extractionThe resulting mixture is extracted with EtOAc (3×100 mL)
  4. washThe organic phase is sequentially washed with water (2×40 mL) and saturated aqueous sodium chloride (1×40 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent is evaporated under reduced pressure
  8. customto yield the crude product which
  9. customis purified by column chromatography on silica gel, eluent 33% EtOAc in hexane
  10. customrecrystallised from diethylether-hexane

Sources & evidence

ORD record
ord-073d08fd76724ab19119862afe427a02
Source dataset
uspto-grants-2006_06
Patent number
US07067543B2

Linked notes

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