Hydrochloric Acid → Piclamilast

HRID 356889Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 356889
[H-].[Na+].[NH2:3][C:4]1[C:9]([Cl:10])=[CH:8][N:7]=[CH:6][C:5]=1[Cl:11].[CH:12]1([O:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=2[O:27][CH3:28])[C:21](Cl)=[O:22])[CH2:16][CH2:15][CH2:14][CH2:13]1.Cl>O1CCCC1.ClCCl>[Cl:11][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([Cl:10])[C:4]=1[NH:3][C:21](=[O:22])[C:20]1[CH:24]=[CH:25][C:26]([O:27][CH3:28])=[C:18]([O:17][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[CH:19]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 898884-Amino-3,5-dichloropyridineHCID 27946003-(Cyclopentyloxy)-4-methoxybenzoyl chloride

Produkt 1

HCID 154575Piclamilast

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

A suspension of sodium hydride (60% dispersion in oil; 2.2 g) in dry tetrahydrofuran (25 mL) at 15°-20° C. is treated portionwise with a solution of 4-amino-3,5-dichloropyridine (4.5 g; that is prepared as described in Reference Example 5) in dry tetrahydrofuran (40 mL), with cooling. The mixture is stirred for a further 30 minutes, and then it is cooled to 10° C. and treated with a solution of 3-cyclopentyloxy-4-methoxybenzoyl chloride (6.4 g) in dry tetrahydrofuran (40 mL), dropwise, during 45 minutes at 10° C. The mixture is stirred at 10° C. for 30 minutes and is then treated with dilute hydrochloric acid (50 mL; 1 N), followed by dichloromethane (75 mL). The layers are separated and the aqueous layer is washed with a further quantity of dichloromethane (25 mL). The combined organic layers are washed with water (50 mL), with saturated aqueous sodium bicarbonate solution (100 mL), and with water (50 mL), dried over magnesium sulfate and evaporated to dryness. The resulting residue is recrystallized from isopropanol, to give N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide (7.0 g).

Aufarbeitung

  1. customthat is prepared
  2. temperaturewith cooling
  3. waitdropwise, during 45 minutes at 10° C
  4. stirringThe mixture is stirred at 10° C. for 30 minutes
  5. customThe layers are separated
  6. washthe aqueous layer is washed with a further quantity of dichloromethane (25 mL)
  7. washThe combined organic layers are washed with water (50 mL), with saturated aqueous sodium bicarbonate solution (100 mL)
  8. dry with materialwith water (50 mL), dried over magnesium sulfate
  9. customevaporated to dryness
  10. customThe resulting residue is recrystallized from isopropanol

Quellen und Nachweise

ORD-Eintrag
ord-be6e0811f31147d1bb4eb5569a80747c
Quelldatensatz
uspto-grants-1998_11
Patentnummer
US05840724

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