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 1802194Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1802194
[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

Komponenten

7

Edukt 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

Produkt 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-carboxamideAusbeute 17,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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+).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-64a2296eda6f4140bf7d5ca0b2b4fbbc
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08349824B2

Notizen zur Reaktion

Wird geladen…