3,3,3-Trifluoropropylamine → 7-(4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxamido)-N-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyridine-2-carboxamide

HRID 1802194Notes

Reaction equation

HRID 1802194 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]([OH:26])=O)[N:23]=[C:17]3[CH:16]=2)=[O:13])=[O:6])[CH2:4][CH2:3][CH2:2]1.[F:28][C:29]([F:34])([F:33])[CH2:30][CH2:31][NH2:32].C(N(C(C)C)C(C)C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(=O)(O)[O-].[Na+]>O1CCCC1>[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]([NH:32][CH2:31][CH2:30][C:29]([F:34])([F:33])[F:28])=[O:26])[N:23]=[C:17]3[CH:16]=2)=[O:13])=[O:6])[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 5

HCID 100013,3,3-TrifluoropropylamineHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 516892Sodium BicarbonateHCID 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 573777447-(4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxamido)-N-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyridine-2-carboxamideYield 17.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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 (140 mg, 0.379 mmole), 3,3,3-trifluoropropan-1-amine (214 mg, 1.9 mmole), N-ethyldiisopropylamine (265 ul, 1.52 mmole) and 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate, 569 ul, 0.948 mmole) in tetrahydrofurane (7 ml) is stirred for 10 h at roomtemperature. The reaction mixture is poured on sat. aqueous sodium bicarbonate solution (60 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layer is washed once with water, once with brine, dried with magnesium sulfate and the solvent is removed in vacuo. Purification of the residue by chromatography on a 12 g silica cartridge (eluent dichloromethane+2% methanol) affords 7-(4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxamido)-N-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyridine-2-carboxamide (31 mg, 17.6%) as a white foam. MS: m/z=465.3 (M+H+).

Workup

  1. extractionextracted with ethyl acetate (2×50 ml)
  2. washThe combined organic layer is washed once with water, once with brine
  3. dry with materialdried with magnesium sulfate
  4. customthe solvent is removed in vacuo
  5. customPurification of the residue by chromatography on a 12 g silica cartridge (eluent dichloromethane+2% methanol)

Sources & evidence

ORD record
ord-64a2296eda6f4140bf7d5ca0b2b4fbbc
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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