3-Cyclopentyloxy-4-methoxybenzamide → Piclamilast

HRID 356888Notes

Reaction equation

HRID 356888 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[O:16][CH3:17])[C:10]([NH2:12])=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([Cl:32])[C:30]=1Cl>C1(C)C=CC=CC=1>[Cl:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([Cl:32])[C:30]=1[NH:12][C:10](=[O:11])[C:9]1[CH:13]=[CH:14][C:15]([O:16][CH3:17])=[C:7]([O:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH:8]=1

Participants

5

Reactant 3

HCID 27793303-Cyclopentyloxy-4-methoxybenzamideHCID 37865313,4,5-TrichloropyridineHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 154575Piclamilast

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Alternatively, a suspension of 3-cyclopentyloxy-4-methoxybenzamide (2.58 g; that is prepared as described in Reference Example 73) in dry toluene (40 mL) is heated at reflux and treated with potassium t-butoxide (1.4 g), followed by 3,4,5-trichloro-pyridine (1.82 g). The mixture is then heated at reflux for 3 hours and 45 minutes, and is then treated with a further quantity of potassium t-butoxide (1.4 g) and heated at reflux for a further period of 7 hours. The mixture is allowed to cool and is then filtered. The filtrate is evaporated and the resulting residue is extracted with aqueous sodium hydroxide solution (2 M). The alkaline solution is then acidified by treatment with acetic acid, and the solid which separates is collected by filtration, washed with water and dried, to give N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxy-benzamide (2.09 g) in the form of a buff solid, m.p. 153°-155° C.

Workup

  1. customthat is prepared
  2. temperatureis heated
  3. temperatureat reflux
  4. temperatureThe mixture is then heated
  5. temperatureat reflux for 3 hours and 45 minutes
  6. temperatureheated
  7. temperatureat reflux for a further period of 7 hours
  8. temperatureto cool
  9. filtrationis then filtered
  10. customThe filtrate is evaporated
  11. extractionthe resulting residue is extracted with aqueous sodium hydroxide solution (2 M)
  12. filtrationthe solid which separates is collected by filtration
  13. washwashed with water
  14. customdried

Sources & evidence

ORD record
ord-a72c4db6d254465ba5bd275d8247e121
Source dataset
uspto-grants-1998_11
Patent number
US05840724

Reaction notes

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