Potassium Carbonate → 1,1-dimethylethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

HRID 2080330Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2080330
Cl.Br[C:3]1[CH:4]=[C:5]([CH2:10][NH2:11])[CH:6]=[CH:7][C:8]=1[F:9].[CH3:12][C:13]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=2)[CH2:21][C@@H:20]1[CH3:35])=[O:18])([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.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>[NH2:11][CH2:10][C:5]1[CH:6]=[CH:7][C:8]([F:9])=[C:3]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([CH2:25][N:22]3[CH2:23][CH2:24][N:19]([C:17]([O:16][C:13]([CH3:15])([CH3:14])[CH3:12])=[O:18])[C@@H:20]([CH3:35])[CH2:21]3)[CH:27]=2)[CH:4]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 27249011-(3-Bromo-4-fluorophenyl)methanamine hydrochlorideHCID 25132855{3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid

Produkt 1

HCID 251325161,1-dimethylethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylateAusbeute 37,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution of [(3-bromo-4-fluorophenyl)methyl]amine hydrochloride (1.68 g, 7 mmol) in dioxane/H2O (10 mL/3.3 mL) was added {3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid (2.33 g, 7 mmol), K2CO3 (4.83, 35 mmol) and Pd(PPh3)4 (405 mg, 0.35 mmol). The resulting mixture was heated at 150° C. in a pressure vessel for 2 hours, then cooled to rt and diluted with EtOAc (50 mL). The organic layer was collected and the aqueous layer was extracted by EtOAc (30 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by Gilson preparatory HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 90/10, v/v, over 12 min), to give the title compound (1.08 g, 37%). LC/MS: m/z, 414 (M+H), 1.83 min.

Aufarbeitung

  1. temperaturecooled to rt
  2. customThe organic layer was collected
  3. extractionthe aqueous layer was extracted by EtOAc (30 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Gilson preparatory HPLC
  8. washeluting with acetonitrile/water/0.1% TFA (10/90 to 90/10

Quellen und Nachweise

ORD-Eintrag
ord-0ca4abd654c54d1ab340093a7dd43ca1
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07932247B2

Notizen zur Reaktion

Wird geladen…