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Methanol → HCID 59627738, Verbindung

HRID 1930105
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1930105
Cl[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([CH3:11])=[N:4][C:3]=1[CH3:12].[Cl:13][C:14]1[CH:19]=[C:18]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH:17]=[CH:16][C:15]=1[C:25]1[C:30]([F:31])=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][C:26]=1[F:41].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CO>COCCOC.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].C(Cl)Cl.O>[C:8]([C:6]1[N:7]=[C:2]([C:28]2[CH:27]=[C:26]([F:41])[C:25]([C:15]3[CH:16]=[CH:17][C:18]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:19][C:14]=3[Cl:13])=[C:30]([F:31])[CH:29]=2)[C:3]([CH3:12])=[N:4][C:5]=1[CH3:11])(=[O:9])[NH2:10]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 579920346-Chloro-3,5-dimethylpyrazine-2-carboxamide2×HCID 59627631HCID 59627631, Verbindung2×

Produkt 1

HCID 59627738HCID 59627738, VerbindungAusbeute 53,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysator
HCID 962WaterLösungsmittel
HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 6-chloro-3,5-dimethylpyrazine-2-carboxamide (Intermediate A) (228 mg, 1.23 mmol) and methyl 2-(2-chloro-2′,6′-difluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-yl)acetate (Intermediate 2-2; 521 mg, 1.23 mmol) and potassium phosphate, tri-basic (314 mg, 1.48 mmol) in DME (15 mL), MeOH (3.75 mL) and water (3.75 mL) was thoughroughly degassed. The mixture was treated with PdCl2(dppf)-DCM adduct (50.3 mg, 0.06 mmol), degassed again and the atmosphere replaced with nitrogen before being heated to 80° C. for 17 hours. The reaction mixture was allowed to cool to room temperature and then evaporated. The crude product was partitioned between EtOAc (75 mL), and 2M HCl (50 mL), the aqueous phase was extracted with a further 80 mL of EtOAc. The organic extracts were combined, dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 70% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-2′,6′-difluorobiphenyl-4-yl)acetate (295 mg, 53.7%) as a white solid.

Aufarbeitung

  1. customdegassed again
  2. temperatureto cool to room temperature
  3. customevaporated
  4. customThe crude product was partitioned between EtOAc (75 mL), and 2M HCl (50 mL)
  5. extractionthe aqueous phase was extracted with a further 80 mL of EtOAc
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 10 to 70% EtOAc in isohexane
  11. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-5130ac02f1204963946ec9218d1679dc
Quelldatensatz
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08188092B2

Notizen zur Reaktion

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