2-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one → 3-Chloro-4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide

HRID 1676711

Reaktionsgleichung

Reaktionsgleichung von HRID 1676711
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[Cl:39]>C(O)C.O.Cl>[Cl:39][C:24]1[CH:25]=[C:26]([CH:37]=[CH:38][C:23]=1[NH:22][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1)[C:27]([NH:29][CH:30]1[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]1)=[O:28]

Komponenten

4

Edukt 2

HCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneHCID 580150334-amino-3-chloro-N-(1-methyl-4-piperidyl)benzamide

Produkt 1

HCID 252535263-Chloro-4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamideAusbeute 16 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 86604601Ethanol water hydrochloric acidLösungsmittel

Versuchsvorschrift

A mixture of 0.1 g (0.32 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20) and 0.1 g (0.38 mmole) of 4-amino-3-chloro-N-(1-methyl-piperidin-4-yl)-benzamide in 10 mL of ethanol-water-hydrochloric acid (20:80:1) was refluxed for 18 hours, and then heated in a pressure tube at 130 degrees for 3 hours. After removal of the solvents under reduced pressure, dichloromethane and saturated sodium carbonate were added. The mixture was extracted with dichloromethane twice. The combined organic layers were washed three times with sodium carbonate, three times with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-75:25) gave 0.028 g of 3-chloro-4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide (I-179) as a white solid.

Aufarbeitung

  1. temperaturewas refluxed for 18 hours
  2. temperatureheated in a pressure tube at 130 degrees for 3 hours
  3. customAfter removal of the solvents under reduced pressure, dichloromethane and saturated sodium carbonate
  4. additionwere added
  5. extractionThe mixture was extracted with dichloromethane twice
  6. washThe combined organic layers were washed three times with sodium carbonate, three times with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by silica gel chromatography
  11. washeluting with dichloromethane-methanol (gradient, 100:0-75:25)

Quellen und Nachweise

ORD-Eintrag
ord-848044aa099847918bdd48c87f4d45e1
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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