Diisopropylethylamine → 4-(3-fluoroazetidine-1-carbonyl)-1-methyl-N-(2-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide

HRID 1802224Notes

Reaction equation

HRID 1802224 reaction equation
[CH3:1][N:2]1[C:6]([C:7](=[O:24])[NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([C:18]4[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=4)[N:17]=[C:11]3[CH:10]=2)=[C:5]([C:25](O)=[O:26])[CH:4]=[N:3]1.Cl.[F:29][CH:30]1[CH2:33][NH:32][CH2:31]1.CCCP(=O)=O.C(N(CC)C(C)C)(C)C>O1CCCC1>[F:29][CH:30]1[CH2:33][N:32]([C:25]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[C:6]=2[C:7]([NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([C:18]4[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=4)[N:17]=[C:11]3[CH:10]=2)=[O:24])=[O:26])[CH2:31]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 101250543-fluoroazetidine HydrochlorideHCID 16167369Propylphosphoric anhydrideHCID 677759501-methyl-5-(2-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 573779604-(3-fluoroazetidine-1-carbonyl)-1-methyl-N-(2-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamideYield 38.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-methyl-5-(2-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid (100 mg, 223 μmol), 3-fluoroazetidine hydrochloride (74.7 mg, 669 μmol), propylphosphonic anhydride (50% in ethyl acetate, 329 μl, 558 μmol) and N,N-diisopropylethylamine (228 μl, 1.34 mmol) in tetrahydrofurane (7 ml) is stirred for 18 hours room temperature. The solvent is evaporated and the residue triturated with sat. aqueous sodium bicarbonate solution. The solid is collected by filtration, washed with water and dried affording 4-(3-fluoroazetidine-1-carbonyl)-1-methyl-N-(2-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide (36 mg, 37.3%) as a light brown solid. mp.: 247-9° C. MS: m/z=421.1 (M+H+).

Workup

  1. customThe solvent is evaporated
  2. customthe residue triturated with sat. aqueous sodium bicarbonate solution
  3. filtrationThe solid is collected by filtration
  4. washwashed with water
  5. customdried

Sources & evidence

ORD record
ord-8ffbea9942884a64a9ed4baf15638c5b
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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