Water → 5-Chloro-2-(2-(tetrahydropyran-4-yl)aminoanilin-5-yl)benzoxazole

HRID 74283

Reaction equation

HRID 74283 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](F)=[C:14]([N+:16]([O-])=O)[CH:15]=3)=[N:7][C:6]=2[CH:20]=1.[NH2:21][CH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.O.[H][H]>C(#N)C.[C].[Pd]>[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:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[C:14]([CH:15]=3)[NH2:16])=[N:7][C:6]=2[CH:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 4192234-AminotetrahydropyranHCID 674975535-Chloro-2-(2-fluoronitrobenzen-5-yl)benzoxazoleHCID 178418361HCID 178418361, compound

Product 1

HCID 674984215-Chloro-2-(2-(tetrahydropyran-4-yl)aminoanilin-5-yl)benzoxazoleYield 49%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To a suspension of 5-chloro-2-(2-fluoronitrobenzen-5-yl)benzoxazole (see Working Example 100-1) (5.00 g, 17.1 mmol) in acetonitrile (20 mL) was added 4-aminotetrahydropyran (3.81 g, 38.0 mmol), and this was heated to reflux for 3 hours. After the reaction was complete, this was cooled to room temperature, water was added, and the precipitated crystals were filtered, washed with water and then dried. To a solution of the crystals obtained in a solvent mixture of methanol/tetrahydrofuran (1:1, 100 mL) was added 10% palladium-carbon (500 mg). A hydrogen atmosphere was substituted in the flask, and this was stirred at room temperature overnight. After the reaction was complete, this was filtered through Celite, the filtrate was concentrated, and the residue obtained was purified by silica gel column chromatography to yield the title compound (2.86 g, 49% yield) as yellowish-brown crystals.

Workup

  1. temperaturethis was heated
  2. temperatureto reflux for 3 hours
  3. filtrationthe precipitated crystals were filtered
  4. washwashed with water
  5. customdried
  6. customTo a solution of the crystals obtained in a solvent mixture of methanol/tetrahydrofuran (1:1, 100 mL)
  7. filtrationthis was filtered through Celite
  8. concentrationthe filtrate was concentrated
  9. customthe residue obtained
  10. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5316f5fc15264fd8ac7f4d857b88507c
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Linked notes

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