Ethyl Acetate → 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)benzoic acid

HRID 716647Notes

Reaction equation

HRID 716647 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][C:19]2C=[CH:25][CH:24]=[CH:23][C:20]=2C#N)=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.[OH-].[Na+].[C:29]([O:32]CC)(=[O:31])[CH3:30]>O1CCOCC1>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:20]=[CH:23][CH:24]=[CH:25][C:30]=2[C:29]([OH:32])=[O:31])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 593144562-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)benzonitrile

Product 1

HCID 593144592-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)benzoic acidYield 76%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzonitrile (80 g, 218 mmol) was dissolved in 1,4-dioxane (1.5 L) and 1 M NaOH (1500 mL, 1500 mmol) was added. The suspension was refluxed overnight. After cooling to RT, ethyl acetate (1 L) was added and layers were separated. The water layer was washed with 1 L of ethyl acetate. Both organic layers were combined and backwashed with 0.1 M NaOH (1 L) until no product was observed in organic. The organics were then discarded. Combined aqueous were then washed with 1 L of ethyl acetate. The water layer was then acidified with acetic acid (very slowly to ph˜7). The solid was filtered and 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid (67 g, 165 mmol, 76% yield) was isolated as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (d, J=6.57 Hz, 6H) 2.11 (s, 3H) 4.41 (quin, J=6.57 Hz, 1H) 5.96 (s, 1H) 6.83 (s, 1H) 7.09 (ddd, J=8.02, 5.12, 3.03 Hz, 1H) 7.40 (1H) 7.52-7.61 (m, 2H) 7.91-8.16 (m, 2H) 8.55 (s, 1H) 10.17 (brs, 1H) 13.64 (brs, 1H); HPLC Rt=2.35 min, MS (ESI): [M+H]+=386.1.

Workup

  1. temperatureThe suspension was refluxed overnight
  2. customlayers were separated
  3. washThe water layer was washed with 1 L of ethyl acetate
  4. washCombined aqueous were then washed with 1 L of ethyl acetate
  5. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-0e4833c377bb44eab46f7528c4276c2b
Source dataset
uspto-grants-2015_11
Patent number
US09192604B2

Reaction notes

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