Diisopropylethylamine → 4-(3-fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide

HRID 1802226Notes

Reaction equation

HRID 1802226 reaction equation
[CH:1]([C:4]1[N:24]=[C:7]2[CH:8]=[C:9]([NH:12][C:13]([C:15]3[N:19]([CH3:20])[N:18]=[CH:17][C:16]=3[C:21](O)=[O:22])=[O:14])[CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2].Cl.[F:26][CH:27]1[CH2:30][NH:29][CH2:28]1.CCCP(=O)=O.C(N(C(C)C)CC)(C)C>O1CCCC1>[CH:1]([C:4]1[N:24]=[C:7]2[CH:8]=[C:9]([NH:12][C:13]([C:15]3[N:19]([CH3:20])[N:18]=[CH:17][C:16]=3[C:21]([N:29]3[CH2:30][CH:27]([F:26])[CH2:28]3)=[O:22])=[O:14])[CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 101250543-fluoroazetidine HydrochlorideHCID 16167369Propylphosphoric anhydrideHCID 677767115-(2-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid

Product 1

HCID 573780664-(3-fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amideYield 86.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 5-(2-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid (70 mg, 213 μmol), 3-fluoroazetidine hydrochloride (71.3 mg, 640 mmol), propylphosphonic anhydride (50% in ethyl acetate, 314 μl, 533 μmol) and diisopropylethylamine (223 μl, 1.28 mmol) in tetrahydrofuran (4 ml) was stirred for 2.5 days (weekend) at 25° C. The solvent was evaporated, the residue was triturated with sodium hydrogencarbonate solution. The precipitated solid was filtered off, washed with water and dried affording 4-(3-fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide (71 mg, 86.4%) as a white solid. mp: 226-227° C., MS: m/z=384.0 (M−H+)

Workup

  1. customThe solvent was evaporated
  2. customthe residue was triturated with sodium hydrogencarbonate solution
  3. filtrationThe precipitated solid was filtered off
  4. washwashed with water
  5. customdried

Sources & evidence

ORD record
ord-c86468a5798e40ebbae77ad2af47e4e3
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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