Sodium Carbonate → (R)-tert-butyl 1-(3-(nicotinamido)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 408334

Reaktionsgleichung

Reaktionsgleichung von HRID 408334
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:17]1[C:18]([N:35]2[CH2:40][CH2:39][CH2:38][C@@H:37]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:36]2)=[C:19]2[C:25]([NH:26][C:27](=[O:34])[C:28]3[CH:33]=[CH:32][CH:31]=[N:30][CH:29]=3)=[CH:24][NH:23][C:20]2=[N:21][CH:22]=1.CC#N.O>O1CCOCC1.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>[C:27]([NH:26][C:25]1[C:19]2[C:20](=[N:21][CH:22]=[C:17]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:18]=2[N:35]2[CH2:40][CH2:39][CH2:38][C@@H:37]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:36]2)[NH:23][CH:24]=1)(=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[N:30][CH:29]=1

Komponenten

7

Edukt 4

HCID 10340Sodium Carbonate2×HCID 66827Phenylboronic Acid2×HCID 18373917Acetonitrile--water (1/1)HCID 67045441(R)-tert-butyl 1-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Produkt 1

HCID 67045306(R)-tert-butyl 1-(3-(nicotinamido)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateAusbeute 60,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

Phenylboronic acid (28.4 mg, 0.233 mmol), PS-palladium tetrakis (88.2 mg, 0.00970 mmol, 0.10 mmol/1 g) and 2N sodium carbonate (194 μL, 0.388 mmol) were added to (R)-tert-butyl 1-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (100 mg, 0.194 mmol; Example 1A, Step 1) in degassed dioxane (1 mL). The reaction was heated to 150° C. for 1 hour under microwave irradiation. Phenylboronic acid (28.4 mg, 0.233 mmol) and 2N sodium carbonate (194 μL, 0.388 mmol) were added, and the reaction was heated to 150° C. for an additional 2 hours under microwave irradiation and then cooled down and filtered. The filtrate was diluted with DCM, dried with MgSO4, filtered, and concentrated. The resulting residue was purified by reverse phase chromatography (Biotage Horizon, C-18 25M+, 10-90% CH3CN/water) to yield (R)-tert-butyl 1-(3-(nicotinamido)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (60 mg, 60% yield) as a solid.

Aufarbeitung

  1. temperaturethe reaction was heated to 150° C. for an additional 2 hours under microwave irradiation
  2. temperaturecooled down
  3. filtrationfiltered
  4. additionThe filtrate was diluted with DCM
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by reverse phase chromatography (Biotage Horizon

Quellen und Nachweise

ORD-Eintrag
ord-1f20b647bd5b472dbf75ccb330868cde
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08758830B2

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