Triethylamine → 7-chloro-2-[1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-1H-[1,2,4]triazol-3-ylethynyl]-[1,2,4]triazolo[1,5-a]pyridine

HRID 1054950Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1054950
[C:1]([C:3]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)[N:5]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:4]=1)#[CH:2].Br[C:23]1[N:32]=[C:26]2[CH:27]=[C:28]([Cl:31])[CH:29]=[CH:30][N:25]2[N:24]=1.C(N(CC)CC)C>O1CCCC1.[Cu]I.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:31][C:28]1[CH:29]=[CH:30][N:25]2[N:24]=[C:23]([C:2]#[C:1][C:3]3[N:7]=[C:6]([N:8]4[CH2:12][CH2:11][CH2:10][CH2:9]4)[N:5]([CH2:13][C:14]4[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=4)[N:4]=3)[N:32]=[C:26]2[CH:27]=1

Komponenten

8

Edukt 3

HCID 8471TriethylamineHCID 838953032-Bromo-7-chloro-(1,2,4)triazolo(1,5-a)pyridineHCID 900255173-ethynyl-1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-1H-[1,2,4]triazole

Produkt 1

HCID 900185777-chloro-2-[1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-1H-[1,2,4]triazol-3-ylethynyl]-[1,2,4]triazolo[1,5-a]pyridineAusbeute 28,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11776TriphenylphosphineKatalysator2×HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator2×HCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysator2×HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A mixture of 3-ethynyl-1-(4-methoxybenzyl)-5-(pyrrolidin-1-yl)-1H-1,2,4-triazole (75 mg, 266 μmol, Eq: 1.00), 2-bromo-7-chloro-[1,2,4]triazolo[1,5-a]pyridine (67.9 mg, 292 μmol, Eq: 1.1) and triethylamine (40.3 mg, 55.5 μl, 398 μmol, Eq: 1.5) in tetrahydrofuran (2 ml) was purged with argon, then copper (I) iodide (1.01 mg, 5.31 μmol, Eq: 0.02), bis(triphenylphosphine) palladium(II) chloride (3.73 mg, 5.31 μmol, Eq: 0.02) and triphenylphosphine (1.39 mg, 5.31 μmol, Eq: 0.02) were added, the vessel was capped and heated for 18 hours to 75° C. Still starting material. The mixture was cooled, purged with argon and another portion of copper (I) iodide (1.01 mg, 5.31 μmol, Eq: 0.02), bis(triphenylphosphine) palladium(II) chloride (3.73 mg, 5.31 μmol, Eq: 0.02) and triphenylphosphine (1.39 mg, 5.31 μmol, Eq: 0.02) was added and the mixture was stirred again over night at 75° C. The crude material was applied on silicagel and purified by flash chromatography over a 20 g silicagel column using ethyl acetate/methanol 0-10% as eluent affording 7-chloro-2-[1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-1H-[1,2,4]triazol-3-ylethynyl]-[1,2,4]triazolo[1,5-a]pyridine (33 mg 26.8%) as an orange oil. MS: m/e=434.4 (M+H+)

Aufarbeitung

  1. customwas purged with argon
  2. customthe vessel was capped
  3. temperatureheated for 18 hours to 75° C
  4. temperatureThe mixture was cooled
  5. custompurged with argon
  6. custompurified by flash chromatography over a 20 g silicagel column

Quellen und Nachweise

ORD-Eintrag
ord-116408cbb52445c582c3853219769096
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394311B2

Notizen zur Reaktion

Wird geladen…