Diisopropylethylamine → 1-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)-3-(5-(trifluoromethyl)pyridin-2-ylthio)pyrazin-2(1H)-one

HRID 562600Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 562600
O[C:2]1[C:3](=[O:21])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([CH3:20])[CH:9]=2)[CH:5]=[CH:6][N:7]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[F:64][C:65]([F:74])([F:73])[C:66]1[CH:67]=[CH:68][C:69]([SH:72])=[N:70][CH:71]=1>CN(C=O)C.C([O-])(O)=O.[Na+]>[OH:19][C:16]([CH3:18])([CH3:17])[CH2:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([N:4]2[CH:5]=[CH:6][N:7]=[C:2]([S:72][C:69]3[CH:68]=[CH:67][C:66]([C:65]([F:64])([F:73])[F:74])=[CH:71][N:70]=3)[C:3]2=[O:21])=[CH:9][C:10]=1[CH3:20]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 178428036HCID 178428036, VerbindungHCID 178506226HCID 178506226, Verbindung

Produkt 1

HCID 251690711-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)-3-(5-(trifluoromethyl)pyridin-2-ylthio)pyrazin-2(1H)-oneAusbeute 14,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A mixture of 3-hydroxy-1-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)pyrazin-2(1H)-one (100 mg, 0.344 mmol), PyBOP (314 mg, 0.603 mmol) and EtN(iPr)2 (0.180 mL, 1.033 mmol) in DMF (6 mL) was stirred at RT for 3 hours prior to addition of 5-(trifluoromethyl)pyridine-2-thiol (74.1 mg, 0.413 mmol). After stirring for 3 days, The reaction was diluted with aq. saturated NaHCO3 (15 ml) prior to extraction with EtOAc (20 ml). The EtOAc layer was dried over Na2SO4 and concentrated. The crude product was purified by prep-HPLC (Phenomenex, Luna 5 micron 30×250 mm, flow rate=30 ml/min., gradient=20% A to 100% B in 30 min., A=90% H2O/10% MeOH/0.1% TFA, B=10% H2O/90% MeOH/0.1% TFA). After concentration, the residue in EtOAc (30 ml) was converted to the free base by washing with aq. saturated NaHCO3 (30 ml). The EtOAc layer was dried over Na2SO4 and concentrated. To yield 1-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)-3-(5-(trifluoromethyl)pyridin-2-ylthio)pyrazin-2(1H)-one (22.76 mg, 14%) as off-white solid. MS (M+1=452). 1H NMR (500 MHz, chloroform-d) δ ppm 8.88 (1H, s), 7.89-7.99 (2H, m), 7.16-7.24 (3H, m), 7.07 (1H, d, J=4.40 Hz), 6.90 (1H, d, J=8.52 Hz), 3.84 (2H, s), 2.30 (3H, s), 1.39 (6H, s).

Aufarbeitung

  1. stirringAfter stirring for 3 days
  2. extractionto extraction with EtOAc (20 ml)
  3. dry with materialThe EtOAc layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by prep-HPLC (Phenomenex, Luna 5 micron 30×250 mm, flow rate=30 ml/min., gradient=20% A to 100% B in 30 min.
  6. concentrationAfter concentration
  7. washby washing with aq. saturated NaHCO3 (30 ml)
  8. dry with materialThe EtOAc layer was dried over Na2SO4
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-ac3b11b5426a4c5a8d7d8f90de58a147
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067420B2

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