Dimethyl Sulfoxide → tert-butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

HRID 1050562Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1050562
[C:1]([C:3]1[N:4]=[CH:5][C:6]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@H:28]2[CH3:41])=[N:7][C:8]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)#[N:2].CS(C)=[O:44].OO.[OH-].[Na+]>CO.CC#N>[C:1]([C:3]1[N:4]=[CH:5][C:6]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])[C@H:28]2[CH3:41])=[N:7][C:8]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)(=[O:44])[NH2:2]

Komponenten

7

Edukt 4

HCID 679Dimethyl SulfoxideHCID 784Hydrogen Peroxide2×HCID 14798Sodium Hydroxide2×HCID 118136128tert-butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

Produkt 1

HCID 118136127tert-butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamateAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

tert-Butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (312) (430 mg, 0.74 mmol) was dissolved in MeOH (25 mL), DMSO (4.4 mL), and TEA (0.22 mL, 1.6 mmol). The solution was cooled to 0° C., and a pre-mixed solution of 30% H2O2 (175 μL, 1.5 mmol) and 4N NaOH (384 μL, 1.5 mmol) was added. The reaction was stirred for 1 hour at 0° C. An additional amount of the pre-mixed solution 30% H2O2 (175 μL, 1.5 mmol) and 4N NaOH (384 μL, 1.5 mmol) was added, and the reaction was stirred for an additional hour at 0° C. MeCN (10 mL) was then added and the solution was stirred for 10 minutes at room temperature. The solvents were removed under reduced pressure, and the residue was subjected to silica flash column chromatography (MeOH/DCM) to give tert-butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (313) (430 mg, 0.74 mmol, 97% yield).

Aufarbeitung

  1. stirringthe reaction was stirred for an additional hour at 0° C
  2. stirringthe solution was stirred for 10 minutes at room temperature
  3. customThe solvents were removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-e8e8c6c753394bf9afc318ff4ddefb59
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09382246B2

Notizen zur Reaktion

Wird geladen…