Isopropanol → 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)-3-trifluoromethoxy-benzamide

HRID 1676713Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676713
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[O:39][C:40]([F:43])([F:42])[F:41].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)(C)C>ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>[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:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]5[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]5)=[O:28])=[CH:25][C:24]=4[O:39][C:40]([F:43])([F:41])[F:42])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

Komponenten

7

Edukt 4

HCID 3776IsopropanolHCID 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 580151524-amino-N-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamide

Produkt 1

HCID 252535274-(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)-3-trifluoromethoxy-benzamideAusbeute 11,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 10340Sodium CarbonateLösungsmittel

Versuchsvorschrift

A mixture of 0.10 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), 0.11 g (0.35 mmole) of 4-amino-N-(1-methyl-piperidin-4-yl)-3-trifluoromethoxy-benzamide, 0.090 g (0.48 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in a pressure tube at 140 degrees overnight, then cooled and diluted with dichloromethane and saturated sodium carbonate. 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, 100:0-60:40) gave 0.022 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-methyl-piperidin-4-yl)-3-trifluoromethoxy-benzamide (I-181) as a white solid.

Aufarbeitung

  1. temperaturewas heated in a pressure tube at 140 degrees overnight
  2. temperaturecooled
  3. extractionThe mixture was extracted twice with dichloromethane
  4. washThe combined organic layers were washed three times with sodium carbonate, three times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel chromatography
  9. washeluting with dichloromethane-methanol (gradient, 100:0-60:40)

Quellen und Nachweise

ORD-Eintrag
ord-d260179dffd349b98d10352203f4ec26
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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