Potassium Carbonate → 3-(5-Amino-3-tert-butyl-pyrazol-1-yl)-5-chloro-benzoic acid ethyl ester

HRID 711147Notes

Reaction equation

HRID 711147 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:17]([O:19][C:20](=[O:29])[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23](Br)[CH:22]=1)[CH3:18]>[Cu]I>[CH2:17]([O:19][C:20](=[O:29])[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([N:7]2[C:8]([NH2:10])=[CH:9][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[N:6]2)[CH:22]=1)[CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 50997988Ethyl 3-Bromo-5-chlorobenzoateHCID 178441179HCID 178441179, compound

Product 1

HCID 1177297563-(5-Amino-3-tert-butyl-pyrazol-1-yl)-5-chloro-benzoic acid ethyl esterYield 19.2%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

3-(Tert-butyl)-1H-pyrazol-5-amine (1.10 g, 7.90 mmol), potassium carbonate (2.29 g, 16.6 mmol), and copper (I) iodide (75.0 mg, 1.58 mmol) were weighed into a microwave vial and purged with argon. 3-Bromo-5-chloro-benzoic acid ethyl ester (2.50 g, 9.49 mmol) was then added, followed by trans-N,N′-dimethylcyclohexane-diamine (225 mg, 1.58 mmol) and the reaction vessel purged with argon. The reagents were then solvated with toluene (8 mL), and then degassed with argon, sealed and subjected to microwave irradiation (135° C., 6 h). The reaction mixture was filtered through Celite, concentrated in vacuo and purified by FCC, eluting with 0-10% EtOAc/cyclohexane, to afford the title compound (489 mg, 19%). LCMS (Method 3) Rt 4.26 min, 322.1 [MH+].

Workup

  1. custompurged with argon
  2. customthe reaction vessel purged with argon
  3. customdegassed with argon
  4. customsealed
  5. customsubjected to microwave irradiation (135° C., 6 h)
  6. filtrationThe reaction mixture was filtered through Celite
  7. concentrationconcentrated in vacuo
  8. custompurified by FCC
  9. washeluting with 0-10% EtOAc/cyclohexane

Sources & evidence

ORD record
ord-73f4d069f7d645589fe7672210300100
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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