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Dimethylamine, hydrochloride → 7-{[4-(azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carbonyl]-amino}-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylic acid dimethylamide

HRID 1802244
Notes
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Reaction equation

HRID 1802244 reaction equation
[N:1]1([C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:27])[C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[C:22]([C:24](O)=[O:25])[N:23]=[C:17]3[CH:16]=2)=[O:13])=[O:6])[CH2:4][CH2:3][CH2:2]1.Cl.[CH3:29][NH:30][CH3:31].CCCP(=O)=O.C(N(C(C)C)CC)(C)C>O1CCCC1>[CH3:29][N:30]([CH3:31])[C:24]([C:22]1[N:23]=[C:17]2[CH:16]=[C:15]([NH:14][C:12]([C:11]3[N:10]([CH3:27])[N:9]=[CH:8][C:7]=3[C:5]([N:1]3[CH2:4][CH2:3][CH2:2]3)=[O:6])=[O:13])[CH:20]=[CH:19][N:18]2[N:21]=1)=[O:25]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 677751337-(4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxamido)-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylic acid

Product 1

HCID 573782897-{[4-(azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carbonyl]-amino}-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylic acid dimethylamide
Yield 40.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of ethyl 7-(4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxamido)-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylate (example 33, step d) (658 mg, 1.66 mmol) and lithium hydroxide hydrate (139 mg, 3.31 mmol) in methanol (20 ml) and water (5 ml) and tetrahydrofuran (10 ml) was stirred for 6 hours at 60° C. (soluble when heated). The mixture was neutralized using hydrochloric acid 2N (1.655 ml, 3.31 mmol) and the mixture was evaporated affording 7-{[4-(azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carbonyl]-amino}-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylic acid (776 mg, 77.4%) as a light brown solid which was used in the following reactions. A mixture of 7-(4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxamido)-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylic acid (120 mg, 244 μmol), dimethylamine hydrochloride (99.4 mg, 1.22 mmol), propylphosphonic anhydride (50% in ethyl acetate, 359 μl, 609 μmol) and diisopropylethylamine (298 μl, 1.71 mmol) in tetrahydrofuran (7 ml) was stirred for 20 hours at 25° C. The solvent was evaporated, the residue was triturated with sodium bicarbonate solution, the precipitated solid was filtered off, washed with water and dried. The material was applied on silicagel and purified by flash chromatography over a 5 g silicagel column using dichloromethane/methanol 5% as eluent affording 7-{[4-(azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carbonyl]-amino}-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylic acid dimethylamide (39 mg, 40.4%) as an off-white foam. MS: m/z=397.1 (M+H+)

Workup

  1. customThe solvent was evaporated
  2. customthe residue was triturated with sodium bicarbonate solution
  3. filtrationthe precipitated solid was filtered off
  4. washwashed with water
  5. customdried
  6. custompurified by flash chromatography over a 5 g silicagel column

Sources & evidence

ORD record
ord-4b6a87213cd2403c97d9f3d4fae6274c
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08349824B2

Reaction notes

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