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

HRID 1516447Notes

Reaction equation

HRID 1516447 reaction equation
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.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[C:42]([O-])([O-])=[O:43].[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].[CH3:42][OH:43].[OH:32][CH:29]1[CH2:30][CH2:31][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:33]6[CH:38]=[CH:37][CH:36]=[CH:35][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])[CH2:27][CH2:28]1

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 67426733{4-[4-(4-Bromo-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-(4-hydroxy-piperidin-1-yl)-methanone

Product 2

HCID 21894508Ammonium hydroxide methanolYield 1%HCID 46834349(4-Hydroxy-piperidin-1-yl)-{4-[4-(4-phenyl-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanoneYield 58%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of {4-[4-(4-bromo-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-(4-hydroxy-piperidin-1-yl)-methanone (0.3 g), benzene-boronic acid (0.086 g) and Na2CO3 (2 M aq, 0.9 mL, degassed), toluene (12 mL, degassed) and EtOH (4 mL) was added to a screw cap pressure flask. To this was added Pd(PPh3)4 (0.02 g), the flask sealed, and the mixture stirred overnight at 110° C. The reaction mixture was then diluted with water, extracted in 10% MeOH-DCM, washed with water and brine, dried over Na2SO4, and the solvent stripped to yield a light brown solid. The solid was flash chromatographed on silica, eluting with DCM:1% NH4OH-MeOH (1000:25) to provide (4-hydroxy-piperidin-1-yl)-{4-[4-(4-phenyl-indol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanone (Compound 17, 0.171 g, 58%) as a white powder. Mp=190-191° C., M+H=496.

Workup

  1. additionwas added to a screw
  2. customcap pressure flask
  3. customthe flask sealed
  4. extractionextracted in 10% MeOH-DCM
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. customto yield a light brown solid
  8. customchromatographed on silica
  9. washeluting with DCM

Sources & evidence

ORD record
ord-85cc25fb3aab42bf912ee2bb2e64c510
Source dataset
uspto-grants-2012_07
Patent number
US08227478B2

Reaction notes

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