Sodium Carbonate → 4-(7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 1676841Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676841
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][NH:7][C:6]=2[N:16]=1.[NH2:17][C:18]1[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[O:23])=[CH:20][C:19]=1[O:34][CH3:35].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C(O)(C)C>[F:14][C:9]1([F:15])[CH2:8][NH:7][C:6]2[N:16]=[C:2]([NH:17][C:18]3[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH:25]4[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]4)=[O:23])=[CH:20][C:19]=3[O:34][CH3:35])[N:3]=[CH:4][C:5]=2[N:11]([CH3:12])[C:10]1=[O:13]

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 866375242-Chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-6H-pyrimido[4,5-b][1,4]diazepin-6-one

Produkt 1

HCID 580150544-(7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamideAusbeute 33,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 0.08 g (0.32 mmole) of 2-chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-292), 0.093 g (0.35 mmole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.092 g (0.48 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in pressure tube at 120 degrees overnight. After cooling, dichloromethane and saturated sodium carbonate were added. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate, times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient, 10:90-100:0) to gave 0.051 g of give 4-(7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-303) as a white solid.

Aufarbeitung

  1. temperaturewas heated in pressure tube at 120 degrees overnight
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted twice with dichloromethane
  4. washThe combined organic layers were washed three times with sodium carbonate, times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by C18 reverse phase silica gel chromatography
  9. washeluting with acetonitrile-water (gradient, 10:90-100:0)

Quellen und Nachweise

ORD-Eintrag
ord-2e92283cd5db4d59920733ccb95d768d
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

Notizen zur Reaktion

Wird geladen…