Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl) pyrazin-2-amine

HRID 1623388

Reaktionsgleichung

Reaktionsgleichung von HRID 1623388
Cl[C:2]1[N:3]=[CH:4][C:5]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:6][C:7]=1[C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([F:15])[CH:9]=1.[C:24]([O-])([O-])=O.[Na+].[Na+].CB(O)O.C(Cl)Cl>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:14][C:13]1[C:8]([C:7]2[N:6]=[C:5]([NH:16][CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH:4]=[N:3][C:2]=2[CH3:24])=[CH:9][C:10]([F:15])=[N:11][CH:12]=1

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 866506355-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

Produkt 1

HCID 669368756-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl) pyrazin-2-amineAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

To a degassed suspension of 5-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (10 mg, 0.028 mmol), Na2CO3 (0.036 ml, 2 M, 0.072 mmol) and methylboronic acid (5 mg, 0.084 mmol) in DME (1 ml) was added PdCl2(dppf).CH2Cl2 adduct (6 mg, 7.35 μmol). The reaction was capped and heated to 105° C. for 4 hr an oil bath. The reaction was diluted with EtOAc and washed with H2O, sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude was purified by column chromatography on silica gel (50% EtOAc/Hexane) to yield 6-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (7 mg, 0.021 mmol, 74.2% yield). LCMS (m/z): 337.2 (MH+), retention time=0.81 min.

Aufarbeitung

  1. customThe reaction was capped
  2. washwashed with H2O
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by column chromatography on silica gel (50% EtOAc/Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-ec73363d320e46d88d70ef91df727b61
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778951B2

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