Sodium Carbonate → HCID 44548920, Verbindung

HRID 1676619Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676619
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:40]=[CH:39][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][F:38])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:41][CH3:42].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(C)C.ClCCl>[CH:16]1([N:7]2[CH2:8][C:9]([F:15])([F:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[CH:40]=[CH:39][C:26]([C:27]([NH:29][CH:30]5[CH2:31][CH2:32][N:33]([CH2:36][CH2:37][F:38])[CH2:34][CH2:35]5)=[O:28])=[CH:25][C:24]=4[O:41][CH3:42])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneHCID 580151444-amino-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide

Produkt 1

HCID 44548920HCID 44548920, VerbindungAusbeute 55,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 0.08 g (0.25 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 0.075 g (0.25 mmole) of 4-amino-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide and 0.072 g (0.38 mmole) of p-toluenesulfonic acid monohydrate in 3 mL of isopropanol was stirred in a sealed tube at 140 degrees overnight. The mixture was cooled, and 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 three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) gave 0.080 g of 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-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide (I-75).

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. extractionThe mixture was extracted twice with dichloromethane
  3. washThe combined organic layers were washed three times with sodium carbonate three times with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography
  8. washeluting with dichloromethane-methanol (gradient, 100:0-90:10)

Quellen und Nachweise

ORD-Eintrag
ord-755e9594f2564b7fb6e7a010f88648b4
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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