Sodium Hydroxide → HCID 53238301, compound

HRID 1966783Notes

Reaction equation

HRID 1966783 reaction equation
C([O:3][C:4](=[O:41])[C:5]([CH3:40])([CH3:39])[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:17]3[CH:23]=[CH:24][C:25]([C:27]4[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=4)=[CH:26][C:16]=3[N:15]=2)=[C:10]([N:34]2[CH:38]=[N:37][CH:36]=[N:35]2)[CH:9]=1)C.[OH-].[Na+]>O1CCOCC1.O>[NH2:33][C:30]1[N:29]=[CH:28][C:27]([C:25]2[CH:24]=[CH:23][C:17]3[N:18]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:14]([C:11]4[CH:12]=[CH:13][C:8]([O:7][CH2:6][C:5]([CH3:39])([CH3:40])[C:4]([OH:41])=[O:3])=[CH:9][C:10]=4[N:34]4[CH:38]=[N:37][CH:36]=[N:35]4)=[N:15][C:16]=3[CH:26]=2)=[CH:32][N:31]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 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 ester

Product 1

HCID 53238301HCID 53238301, compoundYield 70.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 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 (example 66) (95 mg, 0.17 mmol) in 1,4-dioxane (10 mL) and H2O (2 mL) is added 3 M NaOH solution (0.17 mL, 0.52 mmol) at room temperature. The solution is stirred at 65° C. for 6 days. The solution is concentrated and the residue is re-dissolved in H2O (5 mL). The pH of the solution is adjusted to 5 with 12N HCl solution. The milky solution is extracted with EtOAc (3×10 mL). The combined organic layer is dried with MgSO4 (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 (63 mg, 70%). LCMS (ESMS): m/z: 527.40 (M++1).

Workup

  1. concentrationThe solution is concentrated
  2. dissolutionthe residue is re-dissolved in H2O (5 mL)
  3. extractionThe milky solution is extracted with EtOAc (3×10 mL)
  4. dry with materialThe combined organic layer is dried with MgSO4 (500 mg)
  5. filtrationis filtered
  6. concentrationThe filtrate is concentrated
  7. customthe residue is purified by silica gel flash column chromatography with 10% MeOH in CH2Cl2 as the eluent

Sources & evidence

ORD record
ord-d3c22f820afe481c98cfb9b4ea4d6546
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

Loading…