2-Aminophenol → 5-(Benzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazole methanesulfonate

HRID 74169

Reaction equation

HRID 74169 reaction equation
Cl.[CH3:2][C:3]1[N:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:6]2[CH:14]=[CH:15][C:16]([C:18]([OH:20])=O)=[CH:17][C:5]=2[N:4]=1.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1O.CCN=C=NCCCN(C)C.[CH3:40][S:41]([OH:44])(=[O:43])=[O:42]>C(Cl)(Cl)Cl.C(OCC)(=O)C.O.CN(C=O)C>[CH3:40][S:41]([OH:44])(=[O:43])=[O:42].[O:20]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[C:18]1[C:16]1[CH:15]=[CH:14][C:6]2[N:7]([CH:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[C:3]([CH3:2])=[N:4][C:5]=2[CH:17]=1

Participants

9

Reactant 4

HCID 58012-AminophenolHCID 6395Methanesulfonic Acid2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 674984452-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt

Product 1

HCID 866649485-(Benzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazole methanesulfonateYield 29%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt (see Working Example 4-3) (51.2 g, 0.19 mol), 2-aminophenol (24.0 g, 0.21 mol), anhydrous DMF (500 mL) and WSC (45.0 g, 0.23 mol) was stirred for 3 hours under an argon atmosphere. Water (2 L) was added, the solid obtained was filtered off, washed with water, After drying at reduced pressure at 50° C., an obtained solid (45.2 gm 0.13 mol) was dissolved in dioxane (500 mL). Methanesulfonic acid (62.5 g, 0.65 mol) was added thereto and this was stirred at 90° C. for 8 hours. The solvent was concentrated at reduced pressure, water (1 L) was added, and the pH was adjusted to 4 with 1N NaOH. Chloroform (2 L) was added for extraction, and then the aqueous layer was extracted with chloroform (1 L), these were combined and the organic layer was washed with brine (1 L). After MgSO4 drying and filtration, the solvent was concentrated under reduced pressure. The residue obtained was dissolved in chloroform (100 mL) and ethyl acetate (150 mL) and methanesulfonic acid (25.0 g) was added. After stirring awhile in the cold, the precipitated solid was filtered off and this was dried under reduced pressure at 50° C. to yield the title compound (23.7 g, 28.1% yield) as a light purple solid.

Workup

  1. customthe solid obtained
  2. filtrationwas filtered off
  3. washwashed with water
  4. customAfter drying at reduced pressure at 50° C.
  5. dissolutionan obtained solid (45.2 gm 0.13 mol) was dissolved in dioxane (500 mL)
  6. concentrationThe solvent was concentrated at reduced pressure, water (1 L)
  7. additionwas added
  8. additionChloroform (2 L) was added for extraction
  9. extractionthe aqueous layer was extracted with chloroform (1 L)
  10. washthe organic layer was washed with brine (1 L)
  11. filtrationAfter MgSO4 drying and filtration
  12. concentrationthe solvent was concentrated under reduced pressure
  13. customThe residue obtained
  14. stirringAfter stirring awhile in the cold, the precipitated solid
  15. filtrationwas filtered off
  16. customthis was dried under reduced pressure at 50° C.

Sources & evidence

ORD record
ord-69c712b51a2c4f0e95ff1022cc309162
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Linked notes

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