1-Propanol → 5-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl-amino)pyrazine-2-carbonitrile

HRID 1854440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854440
Cl.[S:2]([N:12]1[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25]4)=[N:22][N:23]=3)[C:15]=2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(O)CC.Cl[C:35]1[N:36]=[CH:37][C:38]([C:41]#[N:42])=[N:39][CH:40]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[S:2]([N:12]1[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH:29][C:35]5[N:36]=[CH:37][C:38]([C:41]#[N:42])=[N:39][CH:40]=5)[CH2:25]4)=[N:22][N:23]=3)[C:15]=2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Komponenten

6

Edukt 4

HCID 10311-PropanolHCID 81531DiisopropylethylamineHCID 122957285-Chloropyrazine-2-carbonitrileHCID 69014326(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride

Produkt 1

HCID 580101665-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl-amino)pyrazine-2-carbonitrileAusbeute 81,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a microwave vessel was added (1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride (0.500 g, 1.06 mmol), n-propanol (10 mL), 5-chloropyrazine-2-carbonitrile (0.223 g, 1.60 mmol) and DIEA (0.837 mL, 4.79 mmol). The resulting mixture was heated in a microwave at about 150° C. for about 30 min. DCM (100 mL) was added and a solution was formed. The organic solution was washed with water and brine (50 mL each), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give a brown solid. The residue was taken up in DCM (30 mL) and adsorbed onto silica gel (5 g). The material was purified by silica gel chromatography (80 g cartridge) eluting with neat EtOAc to give 5-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)pyrazine-2-carbonitrile (0.43 g, 80%) as a light yellow solid: LC/MS (Table 2, Method d) Rt=1.40 min; MS m/z: 500 (M+H)+.

Aufarbeitung

  1. customa solution was formed
  2. washThe organic solution was washed with water and brine (50 mL each)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a brown solid
  7. customThe material was purified by silica gel chromatography (80 g cartridge)
  8. washeluting with neat EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-d45f0ff6d6744ed8a068b4eb26a40fa6
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962629B2

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