Sodium Carbonate → (S)-4-(5-(3-fluoro-4-(2-morpholinoethoxy)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine

HRID 1478573Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1478573
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]3[C:19]4=[N:20][C:21]([C:24]5[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=5)=[CH:22][N:23]=[C:18]4[N:17]=[N:16]3)[CH2:9]2)=[N:6][CH:7]=1.[F:30][C:31]1[CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH:43]=[CH:42][C:32]=1[O:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:30][C:31]1[CH:45]=[C:44]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]4[C:19]5=[N:20][C:21]([C:24]6[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=6)=[CH:22][N:23]=[C:18]5[N:17]=[N:16]4)[CH2:9]3)=[N:6][CH:7]=2)[CH:43]=[CH:42][C:32]=1[O:33][CH2:34][CH2:35][N:36]1[CH2:37][CH2:38][O:39][CH2:40][CH2:41]1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 73507291HCID 73507291, VerbindungHCID 1317365094-(2-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenoxy)ethyl)morpholine

Produkt 1

HCID 118364799(S)-4-(5-(3-fluoro-4-(2-morpholinoethoxy)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholineAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

(S)-4-(5-bromopyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine 15 mg (0.033 mmol) was dissolved in dioxane 1 ml, and 4-(2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenoxy)ethyl)morpholine 17 mg (0.049 mmol) and 1M sodium carbonate 98.4 ul (0.098 mmol) were added. Pd(PPh3)4 2 mg (0.0016 mmol) was added, and the mixture was purged with N2 (g), followed by stirring at 105° C. for 4 hours. When the reaction was completed, the reaction mixture was extracted with ethyl acetate and brine, and the organic layer was dried over Na2SO4. Prep LC with 4% MeOH/MC gave a product 7.8 mg (40%).

Aufarbeitung

  1. customthe mixture was purged with N2 (g)
  2. extractionthe reaction mixture was extracted with ethyl acetate and brine
  3. dry with materialthe organic layer was dried over Na2SO4

Quellen und Nachweise

ORD-Eintrag
ord-222052855fbb4c2b9030509a599630f6
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403831B2

Notizen zur Reaktion

Wird geladen…