1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(3-Acetylaminophenyl)-5-(5-chlorobenzoxazol-2-yl)-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74288

Reaction equation

HRID 74288 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:11]=[CH:12][C:13]([NH:17][CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:14]([CH:16]=3)[NH2:15])=[N:7][C:6]=2[CH:24]=1.[C:25]([NH:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)[C:32](O)=O)(=[O:27])[CH3:26].CCN=C=NCCCN(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.CS(O)(=O)=O>[C:25]([NH:28][C:29]1[CH:30]=[C:31]([C:32]2[N:17]([CH:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[C:13]3[CH:12]=[CH:11][C:10]([C:8]4[O:9][C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[CH:24][C:6]=5[N:7]=4)=[CH:16][C:14]=3[N:15]=2)[CH:35]=[CH:36][CH:37]=1)(=[O:27])[CH3:26]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 488473-Acetamidobenzoic acidHCID 516892Sodium Bicarbonate2×HCID 674984215-Chloro-2-(2-(tetrahydropyran-4-yl)aminoanilin-5-yl)benzoxazole

Product 1

HCID 674987982-(3-Acetylaminophenyl)-5-(5-chlorobenzoxazol-2-yl)-1-(tetrahydropyran-4-yl)benzimidazoleYield 14.3%

Reagents, catalysts & solvents 2

HCID 6395Methanesulfonic AcidCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-chloro-2-(2-(tetrahydropyran-4-yl)aminoanilin-5-yl)benzoxazole (see Working Example 100-2) (250 mg, 0.727 mmol) in dimethylformamide (5 mL) was added 3-acetamidobenzoic acid (130 mg, 0.727 mmol) and WSC (167 mg, 0.872 mmol), and this was stirred at room temperature for 23 hours. Saturated aqueous sodium hydrogen carbonate solution was added, the precipitated crystals were filtered, washed with water and then dried. To a solution of the residue obtained in dioxane (5 mL) was added methanesulfonic acid (2 drops), and this was heated to reflux for 3 hours. After the reaction was complete, saturated aqueous sodium hydrogen carbonate solution was added, the precipitated crystals were filtered, washed with water and then dried. The residue obtained was purified by silica gel column chromatography to yield the title compound (50.5 mg, 14%) as white crystals.

Workup

  1. filtrationthe precipitated crystals were filtered
  2. washwashed with water
  3. customdried
  4. customTo a solution of the residue obtained in dioxane (5 mL)
  5. temperaturethis was heated
  6. temperatureto reflux for 3 hours
  7. filtrationthe precipitated crystals were filtered
  8. washwashed with water
  9. customdried
  10. customThe residue obtained
  11. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c614abdbba7f476ea7943da8ace5a6cf
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Linked notes

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