Water → HCID 178502377, Verbindung

HRID 1411332Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1411332
C(OC([NH:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)=O)C1C=CC=CC=1.[CH3:21][O:22][C:23](=[O:48])[NH:24][C@H:25]([C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:46]=[CH:45][C:44](Br)=[CH:43][CH:42]=2)[N:40]=1)=[O:30])[CH:26]([CH3:28])[CH3:27].CN(C)C=O.O.C(=O)(O)[O-].[Na+]>CO.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.[OH-].[OH-].[Pd+2]>[CH3:21][O:22][C:23](=[O:48])[NH:24][C@H:25]([C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:42]=[CH:43][C:44]([C:15]3[CH:14]=[CH:13][C:12]([NH2:11])=[CH:17][CH:16]=3)=[CH:45][CH:46]=2)[N:40]=1)=[O:30])[CH:26]([CH3:28])[CH3:27]

Komponenten

9

Edukt 5

HCID 962WaterHCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27733224-(Benzyloxycarbonylamino)phenylboronic Acid (contains varying amounts of Anhydride)HCID 178502354HCID 178502354, Verbindung

Produkt 1

HCID 178502377HCID 178502377, VerbindungAusbeute 38,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a mixture of 4-(benzyloxycarbonylamino)phenylboronic acid (1.57 g, 5.79 mmol) and ((S)-1-{(S)-2-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.74 g, 3.86 mmol) in N,N-dimethylformamide (30 mL, 400 mmol) was added water (21.91 mL, 1216 mmol) and sodium bicarbonate (2.43 g, 28.96 mmol). The resulting mixture was purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (468 mg, 0.41 mmol) was added. The reaction mixture was purged with nitrogen and then heated at 90° C. overnight. The reaction mixture was cooled to RT, diluted with methanol (10 mL), then filtered. The filtrate was concentrated and the crude product was purified by preparative HPLC to give a white solid. (1.28 g) The crude material was dissolved in methanol (40 mL) and then pumped through a continuous flow hydrogenator at 70° C. using a palladium hydroxide on carbon (20% w/w) cartridge. The resulting solution was concentrated to ˜10 mL, treated with Stratospheres™ PL-CO3 resin and stirred at room temperature for 30 min. The reaction mixture was filtered and the filtrate was concentrated to give the title compound (680 mg).

Aufarbeitung

  1. customThe resulting mixture was purged with nitrogen
  2. customThe reaction mixture was purged with nitrogen
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with methanol (10 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe crude product was purified by preparative HPLC
  8. customto give a white solid
  9. custompumped through a continuous flow hydrogenator at 70° C.
  10. concentrationThe resulting solution was concentrated to ˜10 mL
  11. additiontreated with Stratospheres™ PL-CO3 resin
  12. filtrationThe reaction mixture was filtered
  13. concentrationthe filtrate was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-ec965dfdc36a4bde8ea0511bdab3817e
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921372B2

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