Potassium Carbonate → 4-Methyl-3-[3-[[1-methyl-1-[2-[2-[methyl[(phenylmethoxy)carbonyl]amino]ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzoic acid methyl ester

HRID 337075Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 337075
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[OH:27])([CH3:20])[CH3:19])[C:12]2=[O:28])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:37][CH2:38][N:39]([CH3:50])[C:40](=[O:49])[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(#N)C>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]([CH3:20])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH2:37][CH2:38][N:39]([CH3:50])[C:40]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:49])[CH3:19])[C:12]2=[O:28])[CH:5]=1

Komponenten

5

Edukt 3

HCID 11430Potassium Carbonate2×HCID 13592063Benzyl (2-chloroethyl)methylcarbamate2×HCID 666901483-[3-[[1-(2-Hydroxyphenyl)-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl ester

Produkt 1

HCID 666901444-Methyl-3-[3-[[1-methyl-1-[2-[2-[methyl[(phenylmethoxy)carbonyl]amino]ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzoic acid methyl esterAusbeute 53,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To 3-[3-[[1-(2-Hydroxyphenyl)-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl ester (Example 220b, 2.495 g) in acetonitrile (150 mL) was added potassium carbonate (1.753 g) followed by benzyl 2-chloroethyl(methyl)carbamate (J. Med. Chem., 1992, 35 (17), 3246, 1.660 g) and the reaction heated at 85° C. for 72 h under nitrogen. Further benzyl 2-chloroethyl(methyl)carbamate (0.58 g) and potassium carbonate (0.35 g) were added and the reaction stirred for 2 days. The reaction mixture was cooled, evaporated to dryness and the residue partitioned between water and dichloromethane and the organic layer separated. The aqueous was further extracted with dichloromethane (2×) and the combined organics dried (Na2SO4) and evaporated. Purification (SiO2 chromatography eluting with 40-100% ethyl acetate) gave the subtitle product (1.97 g).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. customevaporated to dryness
  3. customthe residue partitioned between water and dichloromethane
  4. customthe organic layer separated
  5. extractionThe aqueous was further extracted with dichloromethane (2×)
  6. dry with materialthe combined organics dried (Na2SO4)
  7. customevaporated
  8. customPurification (SiO2 chromatography eluting with 40-100% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-bee5f1cdd383470b90bf084f55aca2f2
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889692B2

Notizen zur Reaktion

Wird geladen…