Cesium carbonate → [4-(2-Hydroxy-ethyl)-piperazin-1-yl]-[5-(5-nitro-pyrimidin-2-ylamino)-Pyridin-2-yl]methanone

HRID 1662844

Reaction equation

HRID 1662844 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][C:7]([NH2:10])=[N:8][CH:9]=1)([O-:3])=[O:2].Br[C:12]1[CH:13]=[CH:14][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][OH:28])[CH2:22][CH2:21]2)=[O:19])=[N:16][CH:17]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:28][CH2:27][CH2:26][N:23]1[CH2:22][CH2:21][N:20]([C:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:10][C:7]3[N:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][N:6]=3)=[CH:17][N:16]=2)=[O:19])[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 764905-Nitropyrimidin-2-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58748747(5-Bromo-pyridin-2-yl)-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-methanone

Product 1

HCID 58748708[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-[5-(5-nitro-pyrimidin-2-ylamino)-Pyridin-2-yl]methanoneYield 40%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-nitro-pyrimidin-2-ylamine (0.85 g, 6.1 mmol), intermediate 46 (Example 95) (2.5 g, 8.0 mmol), Pd(OAc)2 (0.40 g, 0.44 mmol), Xantphos (0.5 g, 0.86 mmol) and cesium carbonate (4.0 g, 12 mmol) was suspended in dioxane (30 mL) and heated at reflux under the argon atmosphere for 18 h. The mixture was allowed to cool to room temperature, filtered and washed with DCM. The filtrate was concentrated and the crude product purified by flash chromatography on silica gel (5% MeOH/DCM to 15% MeOH/DCM) to afford the title compound (0.90 g, 40%) as a yellow solid.

Workup

  1. temperatureheated
  2. temperatureat reflux under the argon atmosphere for 18 h
  3. filtrationfiltered
  4. washwashed with DCM
  5. concentrationThe filtrate was concentrated
  6. customthe crude product purified by flash chromatography on silica gel (5% MeOH/DCM to 15% MeOH/DCM)

Sources & evidence

ORD record
ord-34d0626db6e243d694b35cb2bc284c9b
Source dataset
uspto-grants-2011_10
Patent number
US08030487B2

Linked notes

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