1-Pyrrolidineethanamine → 5-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-6-methyl-2-oxo-N-(2-pyrrolidin-1-ylethyl)-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide

HRID 2089249Notes

Reaction equation

HRID 2089249 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:15]=[C:16]([C:32]([O:34]CC)=O)[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[C:19]=3[CH3:20])=[CH:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2].[N:37]1([CH2:42][CH2:43][NH2:44])[CH2:41][CH2:40][CH2:39][CH2:38]1>CO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]([C:14]3[CH:15]=[C:16]([C:32]([NH:44][CH2:43][CH2:42][N:37]4[CH2:41][CH2:40][CH2:39][CH2:38]4)=[O:34])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:29])([F:30])[F:28])[CH:22]=4)[C:19]=3[CH3:20])=[CH:12][CH:11]=[N:10]2)=[CH:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 13441-PyrrolidineethanamineHCID 58218050Ethyl 5-[2-(4-cyanophenyl)-2H-pyrazole-3-yl]-6-methyl-2-oxo-1-(3-trifluoromethylphenyl)-1,2-dihydropyridine-3-carboxylate2×

Product 1

HCID 670925995-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-6-methyl-2-oxo-N-(2-pyrrolidin-1-ylethyl)-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamideYield 67.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 5-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylate (Intermediate A) (200 mg, 0.41 mmol) and 2-pyrrolidin-1-ylethanamine (928 mg, 8.12 mmol, 20 eq) were dissolved in MeOH (2.5 mL) and heated to 100° C. in a sealed vial by a microwave oven for 40 min The solvent was evaporated and EtOH (3 mL) was added and heated to 50° C. for two hours and then water (3 mL) was added and the mixture was stirred at room temperature over night. The precipitate was centrifuged (4000 rpm, 3 min) and washed three times with EtOH/H2O 1:1 (5 mL) and dried over night. The residue was dissolved in acetonitrile and purified by HPLC (30-95% MeOH in H2O+0.1% TFA), the pure fractions were freeze-dried, dissolved in acetonitrile and desalted with Na2CO3 (solid phase) and evaporated to afford 5-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-6-methyl-2-oxo-N-(2-pyrrolidin-1-ylethyl)-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide as a white solid (156 mg, 65%); 1H NMR (500 MHz, DMSO): δ 1.67-1.59 (4H, m), 1.72 (3H, s), 2.43-2.37 (4H, m), 2.49-2.47 (2H, m), 3.38-3.33 (2H, m), 6.72 (1H, d), 7.67-7.63 (2H, m), 7.71 (1H, d), 7.88-7.82 (2H, m), 7.96-7.89 (4H, m), 8.07 (1H, s), 9.35 (1H, t);

Workup

  1. customwas evaporated
  2. additionEtOH (3 mL) was added
  3. temperatureheated to 50° C. for two hours
  4. additionwater (3 mL) was added
  5. custom(4000 rpm, 3 min)
  6. washwashed three times with EtOH/H2O 1:1 (5 mL)
  7. customdried over night
  8. dissolutionThe residue was dissolved in acetonitrile
  9. custompurified by HPLC (30-95% MeOH in H2O+0.1% TFA)
  10. customthe pure fractions were freeze-dried
  11. dissolutiondissolved in acetonitrile
  12. customevaporated

Sources & evidence

ORD record
ord-6b74af3e081e49909fb60ecba8c0a1ec
Source dataset
uspto-grants-2013_05
Patent number
US08436024B2

Reaction notes

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