Ethyl Acetate → 2-methyl-4-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-amide

HRID 1844435Notes

Reaction equation

HRID 1844435 reaction equation
[CH3:1][N:2]1[C:6]([C:7](=[O:24])[NH:8][C:9]2[CH:10]=[CH:11][C:12]3[N:13]([N:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=3)[CH:14]=2)=[C:5]([C:25]([OH:27])=O)[CH:4]=[N:3]1.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1.CCCP(=O)=O.C(OCC)(=O)C.C(N(CC)C(C)C)(C)C>O1CCCC1>[C:18]1([C:16]2[N:17]=[C:12]3[CH:11]=[CH:10][C:9]([NH:8][C:7]([C:6]4[N:2]([CH3:1])[N:3]=[CH:4][C:5]=4[C:25]([N:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[O:27])=[O:24])=[CH:14][N:13]3[N:15]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 715375761-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-6-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 715375772-methyl-4-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-amideYield 35.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-6-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid (112 mg, 309 μmol), pyrrolidine (220 mg, 256 μl, 3.09 mmol), propylphosphonic anhydride in ethyl acetate 50% (492 mg, 455 μl, 773 μmol) and N,N-diisopropylethylamine (120 mg, 158 μl, 927 μmol) in tetrahydrofuran (7.00 ml) was refluxed for 18 hours. The solvent was evaporated, the residue was triturated with saturated aqueous sodium hydrogencarbonate. The precipitated solid was filtered off, washed with water and dried in vacuo, affording 2-methyl-4-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-amide (45 mg, 35%) as brown solid. Mp.: 210° C. MS: m/z=416.1 (M+H+).

Workup

  1. temperaturewas refluxed for 18 hours
  2. customThe solvent was evaporated
  3. customthe residue was triturated with saturated aqueous sodium hydrogencarbonate
  4. filtrationThe precipitated solid was filtered off
  5. washwashed with water
  6. customdried in vacuo

Sources & evidence

ORD record
ord-94823c55a20143a0870b875ba599a246
Source dataset
uspto-grants-2015_02
Patent number
US08946427B2

Reaction notes

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