Cesium carbonate → 5-[1-tert-butyl-2-(2-1,2,3-triazol-2-yl-phenyl)-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine

HRID 1966687Notes

Reaction equation

HRID 1966687 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:11]2[CH:17]=[CH:18][C:19]([C:21]3[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=3)=[CH:20][C:10]=2[N:9]=1.[NH:28]1[CH:32]=[CH:31][N:30]=[N:29]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:13]([N:12]1[C:11]2[CH:17]=[CH:18][C:19]([C:21]3[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=3)=[CH:20][C:10]=2[N:9]=[C:8]1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:29]1[N:30]=[CH:31][CH:32]=[N:28]1)([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 585419535-[2-(2-bromo-phenyl)-1-tert-butyl-1H-benzimidazol-5-yl]-pyrimidin-2-ylamineHCID 178418936HCID 178418936, compound

Product 1

HCID 532362545-[1-tert-butyl-2-(2-1,2,3-triazol-2-yl-phenyl)-1H-benzimidazol-5-yl]-pyrimidin-2-ylamineYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-[2-(2-bromo-phenyl)-1-tert-butyl-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine (refer to example 8, step 1) (57 mg, 0.14 mmol) in DMF (5 mL) are added 1H-1,2,3-triazole (0.012 mL, 0.2 mmol), CuO (1 mg, 0.013 mmol), Fe(acac)3 (14 mg, 0.04 mmol) and Cs2CO3 (88 mg, 0.27 mmol) at room temperature. The mixture is heated at 120° C. for 96 hours and then cooled down and filtered. The filtrate is extracted with H2O (10 mL) and EtOAc (3×10 mL). The combined organic layer is dried with MgSO4 and is filtered. The filtrate is concentrated and the residue is purified by silica gel chromatography eluting with 5% MeOH in CH2Cl2 to afford a less polar product 5-[1-tert-butyl-2-(2-1,2,3-triazol-2-yl-phenyl)-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine (Example 14) (16 mg, 29%) LCMS (ESMS): m/z 411.68 (M++1) as the major product and a more polar product 5-[1-tert-butyl-2-(2-1,2,3-triazol-1-yl-phenyl)-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine (Example 15) (7 mg, 13%) LCMS (ESMS): m/z 411.68 (M++1) as the minor product.

Workup

  1. temperaturecooled down
  2. filtrationfiltered
  3. extractionThe filtrate is extracted with H2O (10 mL) and EtOAc (3×10 mL)
  4. dry with materialThe combined organic layer is dried with MgSO4
  5. filtrationis filtered
  6. concentrationThe filtrate is concentrated
  7. customthe residue is purified by silica gel chromatography
  8. washeluting with 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-9c468a3fd6b54c368d783f81e91c05a1
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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