Lithium N-methylmethanaminide → 2-{[3-Tert-butyl-1-(2-methylphenyl)-1h-pyrazol-5-yl]amino}-4-(dimethylamino)benzoic acid

HRID 915592Notes

Reaction equation

HRID 915592 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]2[CH:19]=[C:18](F)[CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])[N:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[Li][N:29]([CH3:31])[CH3:30]>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]2[CH:19]=[C:18]([N:29]([CH3:31])[CH3:30])[CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])[N:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 5152226Lithium N-methylmethanaminideHCID 589585822-{[3-Tert-butyl-1-(2-methylphenyl)-1h-pyrazol-5-yl]amino}-4-fluorobenzoic acid

Product 1

HCID 589586092-{[3-Tert-butyl-1-(2-methylphenyl)-1h-pyrazol-5-yl]amino}-4-(dimethylamino)benzoic acidYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-fluorobenzoic acid (Example 248, 35 mg, 0.09 mmol) in THF (1 mL) at −40° C. was added LiNMe2 (0.19 mL, 1 M in hexanes) under nitrogen. The mixture was then stirred at this temperature for 30 min, and then gradually warmed to rt over a 4 h period. The pH of the solution was adjusted to pH 5, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude was purified by HPLC using gradient elution from 10 to 80% acetonitrile in water to afford 5.7 mg (15%) of the title compound. 1H NMR (300 MHz, CD2Cl2) δ 9.55 (s, 1H), 7.73 (d, 1H), 7.22-7.35 (m, 4H), 6.44 (d, 1H), 6.18 (dd, 1H), 6.15 (s, 1H), 3.00 (s, 6H), 2.04 (s, 3H), 1.32 (s, 9H). ES-MS m/z 393.2 (MH30 ); HPLC RT (min) 2.84.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified by HPLC
  6. washelution from 10 to 80% acetonitrile in water

Sources & evidence

ORD record
ord-8c2db87082454790adc8c54f20ad1b7c
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

Loading…