Water → (R)-methyl 2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)-4-methylbenzoate

HRID 1631741Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1631741
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH2:12][N:13]2[CH2:22][C@@H:21]3[CH2:23][O:24][CH2:25][CH2:26][N:20]3[C:19]3[N:18]=[C:17]([Cl:27])[N:16]=[CH:15][C:14]2=3)[CH:3]=1.[C:28]([O-])([O-])=O.[K+].[K+].CB1OB(C)OB(C)O1.O>O1CCOCC1.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:27][C:17]1[N:16]=[CH:15][C:14]2[N:13]([CH2:12][C:4]3[CH:3]=[C:2]([CH3:28])[CH:11]=[CH:10][C:5]=3[C:6]([O:8][CH3:9])=[O:7])[CH2:22][C@@H:21]3[CH2:23][O:24][CH2:25][CH2:26][N:20]3[C:19]=2[N:18]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86670124(R)-methyl 4-bromo-2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoate

Produkt 1

HCID 86670125(R)-methyl 2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)-4-methylbenzoateAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(R)-methyl 4-bromo-2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoate (PREPARATION x56, 164 mg, 0.361 mmol), K2CO3 (100 mg, 0.723 mmol), PdCl2(dppf) (13.22 mg, 0.018 mmol) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (0.060 mL, 0.434 mmol) were dissolved in dioxane (2 mL) and water (0.4 mL) to give an orange suspension. The reaction mixture was heated to 100° C. and allowed to stir overnight, then quenched with aqueous saturated NH4Cl. The reaction mixture was diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was then loaded onto an ISCO® silica gel cartridge (12 g) and eluted using an ethyl acetate/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a white foam (102 mg, 73%). ESI-MS m/z [M+H]+ calc'd for C19H21ClN4O3, 389.14. found 389.2.

Aufarbeitung

  1. customquenched with aqueous saturated NH4Cl
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with aqueous saturated NH4Cl (3×15 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washeluted
  8. customThe product was collected
  9. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-5f20ca4b09ff4005a7cdfcf35d74c314
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791107B2

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