Cesium carbonate → 3-{4-[5-(2-Amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzoimidazol-2-yl]-3-[1,2,4]triazol-1-yl-phenoxy}-2,2-dimethyl-propionic acid ethyl ester

HRID 1966782Notes

Reaction equation

HRID 1966782 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:32]=[CH:31][C:11]3[N:12]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:13]([C:15]4[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=4[N:22]4[CH:26]=[N:25][CH:24]=[N:23]4)=[N:14][C:10]=3[CH:9]=2)=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:40][C:41]([CH3:48])([CH3:47])[C:42]([O:44][CH2:45][CH3:46])=[O:43]>CN(C=O)C>[CH2:45]([O:44][C:42](=[O:43])[C:41]([CH3:48])([CH3:47])[CH2:40][O:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[N:12]([C:27]([CH3:29])([CH3:28])[CH3:30])[C:11]3[CH:31]=[CH:32][C:8]([C:5]4[CH:4]=[N:3][C:2]([NH2:1])=[N:7][CH:6]=4)=[CH:9][C:10]=3[N:14]=2)=[C:16]([N:22]2[CH:26]=[N:25][CH:24]=[N:23]2)[CH:17]=1)[CH3:46]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 287572Ethyl 3-chloro-2,2-dimethylpropanoateHCID 1361974594-[5-(2-Amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzoimidazol-2-yl]-3-[1,2,4]-triazol-1-yl-phenol

Product 1

HCID 532383003-{4-[5-(2-Amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzoimidazol-2-yl]-3-[1,2,4]triazol-1-yl-phenoxy}-2,2-dimethyl-propionic acid ethyl esterYield 51.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 4-[5-(2-Amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzoimidazol-2-yl]-3-[1,2,4]-triazol-1-yl-phenol (300 mg, 0.7 mmol) in DMF (10 mL) is added cesium carbonate (687 mg, 2.1 mmol) followed by Ethyl 3-chloro-2,2-dimethylpropanoate (231 mg, 1.4 mmol) at room temperature. The solution is heated to 90° C. for 72 hours. The solution is cooled to room temperature and is extracted with H2O (10 mL) and EtOAc (3×10 mL). The combined organic layer is dried with Mg2SO4 (500 mg) and is filtered. The filtrate is concentrated and the residue is purified by silica gel flash column chromatography with 10% MeOH in CH2Cl2 as the eluent to afford the title compound (200 mg, 51%). LCMS (ESMS): m/z: 555.40 (M++1).

Workup

  1. temperatureThe solution is cooled to room temperature
  2. extractionis extracted with H2O (10 mL) and EtOAc (3×10 mL)
  3. dry with materialThe combined organic layer is dried with Mg2SO4 (500 mg)
  4. filtrationis filtered
  5. concentrationThe filtrate is concentrated
  6. customthe residue is purified by silica gel flash column chromatography with 10% MeOH in CH2Cl2 as the eluent

Sources & evidence

ORD record
ord-b3e7f91bfdc84dee9ca72878bd3d78f4
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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