Potassium Carbonate → 1-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-imidazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

HRID 2366875Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2366875
[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3].CC([N:35]([CH2:39][CH2:40][N:41]1[CH:45]=[C:44](I)[N:43]=[CH:42]1)[C:36](=[O:38])[O-:37])(C)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:44]3[N:43]=[CH:42][N:41]([CH2:40][CH2:39][NH:35][C:36]([O:37][C:16]([CH3:11])([CH3:7])[CH3:15])=[O:38])[CH:45]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3]

Komponenten

7

Edukt 3

HCID 11430Potassium Carbonate2×HCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamateHCID 1317313251,1-dimethylethyl[2-(4-iodo-1H-imidazol-1-yl)ethyl]carbamate

Produkt 1

HCID 681854051-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-imidazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamateAusbeute 12 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 52) (333 mg, 0.80 mmol), 1,1-dimethylethyl[2-(4-iodo-1H-imidazol-1-yl)ethyl]carbamate (for a preparation see Intermediate 80) (270 mg, 0.8 mmol), potassium carbonate (443 mg, 3.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (46 mg, 0.040 mmol) in toluene (10 ml) and ethanol (10 ml) was refluxed under nitrogen for 16 h then cooled to room temperature and the insoluble were filtered off. Potassium carbonate (443 mg, 3.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (46 mg, 0.040 mmol) were added to the filtrate and the resulting mixture refluxed for 7 h then cooled to room temperature and the insoluble filtered off. The resulting solution was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-imidazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (47 mg, 0.094 mmol, 12%) as a light brown solid.

Aufarbeitung

  1. temperaturewas refluxed under nitrogen for 16 h
  2. filtrationthe insoluble were filtered off
  3. temperaturethe resulting mixture refluxed for 7 h
  4. temperaturethen cooled to room temperature
  5. concentrationThe resulting solution was concentrated in vacuo
  6. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-d58d5a6c4db1414795bb17103fd7084a
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697725B2

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