1,3-Dimethyl-1H-pyrazol-5-amine → 2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acid

HRID 1472532Notes

Reaction equation

HRID 1472532 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])[C:5]([Cl:18])=[CH:4][N:3]=1.[CH3:19][N:20]1[C:24]([NH2:25])=[CH:23][C:22]([CH3:26])=[N:21]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:5]1[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])=[CH:7][C:2]([NH:25][C:24]2[N:20]([CH3:19])[N:21]=[C:22]([CH3:26])[CH:23]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 575168952-[(2,5-Dichloro-4-pyridinyl)amino]benzoic acid

Product 1

HCID 462147742-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acidYield 22.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A pressure tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]benzoic acid (1.0 g, 3.53 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (0.589 g, 5.30 mmol), (±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene (0.330 g, 0.530 mmol), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 0.162 g, 0.177 mmol) and sodium tert-butoxide (0.849 g, 8.83 mmol) in 1,4-dioxane (30 mL). The tube was degassed with N2 and sealed and the reaction mixture was heated in an oil bath at 120° C. for 18 hours. The reaction mixture was evaporated to dryness under high vacuum. The residue was taken back in water solution and the pH was adjusted to ˜4 to 5 using 6.0 N hydrochloride acid. The reaction was concentrated to dryness and the resulting solid was dissolved in MeOH and purified by reverse-phase HPLC to give the title compound as a solid (285 mg, 21% yield). MS: M(C17H16ClN5O2)=357.79, (M+H)+=358, 360.

Workup

  1. customThe tube was degassed with N2
  2. customsealed
  3. customThe reaction mixture was evaporated to dryness under high vacuum
  4. concentrationThe reaction was concentrated to dryness
  5. dissolutionthe resulting solid was dissolved in MeOH
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-629ae6c70ed74c26a4e60c3a47bbb256
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

Loading…