Toluene → (4-Hydroxy-piperidin-1-yl)-{4-[4-(4-thiophen-3-yl-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanone

HRID 1516448Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1516448
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:11]1[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]2[CH2:23][CH2:22][CH:21]([C:24]([N:26]3[CH2:31][CH2:30][CH:29]([OH:32])[CH2:28][CH2:27]3)=[O:25])[CH2:20][CH2:19]2)[N:12]=1.[S:33]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34]1.[C:41]([O-])([O-])=[O:42].[Na+].[Na+].C1(C)C=CC=CC=1>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.CCO>[NH4+:6].[OH-:25].[CH3:41][OH:42].[OH:32][CH:29]1[CH2:28][CH2:27][N:26]([C:24]([CH:21]2[CH2:20][CH2:19][CH:18]([NH:17][C:13]3[N:12]=[C:11]([N:6]4[C:7]5[C:3](=[C:2]([C:35]6[CH:36]=[CH:37][S:33][CH:34]=6)[CH:10]=[CH:9][CH:8]=5)[CH:4]=[CH:5]4)[CH:16]=[CH:15][N:14]=3)[CH2:23][CH2:22]2)=[O:25])[CH2:31][CH2:30]1

Komponenten

9

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 67426733{4-[4-(4-Bromo-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-(4-hydroxy-piperidin-1-yl)-methanone

Produkt 2

HCID 21894508Ammonium hydroxide methanolAusbeute 1 %HCID 46834351(4-Hydroxy-piperidin-1-yl)-{4-[4-(4-thiophen-3-yl-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanoneAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of {4-[4-(4-bromo-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-(4-hydroxy-piperidin-1-yl)-methanone (0.51 g), 3-thiophene-boronic acid (0.16 g) and Na2CO3 (2 M aq, 1.53 mL, degassed), toluene (12 mL, degassed) and EtOH (12 mL) was added to a screw cap pressure flask. To this was added Pd(PPh3)4 (0.035 g), the flask sealed, and the mixture stirred overnight at 110° C. The reaction mixture was then diluted with water, extracted in DCM, washed with water and brine, dried over Na2SO4, and the solvent stripped to yield a yellow solid. The solid was flash chromatographed on silica, eluting with DCM:1% NH4OH-MeOH (1000:50) to provide (4-hydroxy-piperidin-1-yl)-{4-[4-(4-thiophen-3-yl-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanone (Compound 18, 0.32 g, 63%) as a light yellow powder. Mp=171-172° C., M+H=502.

Aufarbeitung

  1. additionwas added to a screw
  2. customcap pressure flask
  3. customthe flask sealed
  4. extractionextracted in DCM
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. customto yield a yellow solid
  8. customchromatographed on silica
  9. washeluting with DCM

Quellen und Nachweise

ORD-Eintrag
ord-bc06e09b78bb4b41a56ec99b871f8fa1
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08227478B2

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