Pyridine → N-(5-chloro-pyridin-2-yl)-2-(4-cyano-benzoyl-amino)-5-methoxy-benzamide hydrochloride

HRID 39349

Reaktionsgleichung

Reaktionsgleichung von HRID 39349
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([Cl:9])=[O:8])=[CH:5][CH:4]=1)#[N:2].[NH2:12][C:13]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:14]=1[C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][N:19]=1)=[O:16].N1C=CC=CC=1>C1COCC1>[ClH:9].[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:15](=[O:16])[C:14]2[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:13]=2[NH:12][C:7](=[O:8])[C:6]2[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)=[N:19][CH:20]=1

Komponenten

5

Edukt 3

HCID 1049PyridineHCID 801724-Cyanobenzoyl chlorideHCID 219062412-amino-N-(5-chloropyridin-2-yl)-5-methoxybenzamide

Produkt 1

HCID 66609683N-(5-chloro-pyridin-2-yl)-2-(4-cyano-benzoyl-amino)-5-methoxy-benzamide hydrochlorideAusbeute 75,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
22 °C

Versuchsvorschrift

To a 780 L Hastelloy reactor, was charged 4-cyanobenzoyl chloride (E) (17.2 kg, 1.1 eq.) and THF (92 kg, 3.5 parts). Reactor contents were agitated at 22° C. (19-25° C.) until all of the solids had dissolved. The resulting solution was transferred to a lower receiver and the reactor was rinsed forward with THF (26 kg, 1 part). Compound D (26.4 kg, 1 eq.), THF (396 kg, 15 parts) and pyridine (2.90 kg, 0.4 eq.) were charged to a clean reactor. The pump and lines were rinsed forward with THF (34 kg, 1.3 parts). Via a metering pump, the 4-cyanobenzoyl chloride/THF solution was charged to the reactor, keeping the temperature at <30° C. and rinsing forward with THF (ca. 10 kg). The resulting yellow-colored slurry was agitated at 22° C. (19-25° C.) for ca 2 hrs. In-process HPLC taken after 2 hrs showed a compound of Formula D content of 0%, indicating completion of the reaction. The slurry was filtered onto a pressure nutsche fitted with a filter cloth. The reactor, pump, lines and wet cake were rinsed with three portions of ethanol (ca. 15 kg each). The wet filter cake was discharged (65.4 kg) and transferred back to the reactor for slurry wash in ethanol (317 kg, 12 parts) at 22° C. (19-25° C.) for ca. 1 hr. The slurry was filtered onto the pressure nutsche and the reactor, pump, lines, and wet filter cake were rinsed with two portions of ethanol (ca. 15 kg each) and two portions of THF (ca. 15 kg each). The wet filter cake was dried under vacuum with a maximum temperature of warm glycol bath (to heat the dryer jacket) of 40° C. After 14.5 hrs of drying, LOD was 0.75%. The dried material was milled (screen 0.125″) to give 31.8 kg of product, which was dried under vacuum for another 10.5 hrs. LOD after drying was 1.8%, and the product was discharged (31.5 kg) in 74.8% yield (expected 60-90%). HPLC showed 100% purity.

Aufarbeitung

  1. dissolutionhad dissolved
  2. washthe reactor was rinsed forward with THF (26 kg, 1 part)
  3. washThe pump and lines were rinsed forward with THF (34 kg, 1.3 parts)
  4. additionVia a metering pump, the 4-cyanobenzoyl chloride/THF solution was charged to the reactor
  5. customat <30° C.
  6. washrinsing forward with THF (ca. 10 kg)
  7. stirringThe resulting yellow-colored slurry was agitated at 22° C. (19-25° C.) for ca 2 hrs
  8. customcompletion of the reaction
  9. filtrationThe slurry was filtered onto a pressure nutsche
  10. customfitted with a filter cloth
  11. washThe reactor, pump, lines and wet cake were rinsed with three portions of ethanol (ca. 15 kg each)
  12. washwash in ethanol (317 kg, 12 parts) at 22° C. (19-25° C.) for ca. 1 hr
  13. filtrationThe slurry was filtered onto the pressure nutsche
  14. washthe reactor, pump, lines, and wet filter cake were rinsed with two portions of ethanol (ca. 15 kg each) and two portions of THF (ca. 15 kg each)
  15. customThe wet filter cake was dried under vacuum with a maximum temperature of warm glycol bath (
  16. temperatureto heat the dryer jacket) of 40° C
  17. customAfter 14.5 hrs of drying
  18. customThe dried material was milled (screen 0.125″)

Quellen und Nachweise

ORD-Eintrag
ord-e2cd16ea033b4d35aca7853c3e4acb7d
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524907B2

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