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 588417Notes

Reaction equation

HRID 588417 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-200bc783a5cc4820a38e2edfe34f5a62
Source dataset
uspto-grants-2016_01
Patent number
US09227970B2

Reaction notes

Loading…