2-Methylbenzenesulfonic acid hydrate → 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(tetrahydro-pyran-4-yl)-benzamide

HRID 1676794

Reaktionsgleichung

Reaktionsgleichung von HRID 1676794
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[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:22]=1.O.C1(C)C(S(O)(=O)=O)=CC=CC=1.[NH2:35][C:36]1[CH:50]=[CH:49][C:39]([C:40]([NH:42][CH:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)=[O:41])=[CH:38][CH:37]=1>C(O)(C)C>[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:35][C:36]4[CH:37]=[CH:38][C:39]([C:40]([NH:42][CH:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[O:41])=[CH:49][CH:50]=4)=[N:22][C:6]2=3)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Komponenten

5

Edukt 3

HCID 124969952-Methylbenzenesulfonic acid hydrateHCID 436095624-amino-N-(oxan-4-yl)benzamideHCID 579555542-Chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Produkt 1

HCID 580150524-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(tetrahydro-pyran-4-yl)-benzamideAusbeute 54,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

A mixture of 0.0562 g (0.18 mmole) 2-chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-246), 0.0514 g (0.27 mmole) of toluenesulfonic acid monohydrate, 0.0396 g (0.18 mmole) of 4-amino-N-(tetrahydro-pyran-4-yl)-benzamide and 1 mL of isopropanol was heated in a sealed vessel at 140 degrees for 16.5 hours, cooled and concentrated under reduced pressure. The residue taken up in ethyl acetate and washed successively with 50 mL of saturated aqueous sodium bicarbonate, 50 mL of water, 50 mL of brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from acetonitrile to give 0.0501 g of 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(tetrahydro-pyran-4-yl)-benzamide (I-263) as a white solid.

Aufarbeitung

  1. temperaturewas heated in a sealed vessel at 140 degrees for 16.5 hours
  2. temperaturecooled
  3. concentrationconcentrated under reduced pressure
  4. washwashed successively with 50 mL of saturated aqueous sodium bicarbonate, 50 mL of water, 50 mL of brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was recrystallized from acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-7dd5afab02cd468386c0b803bebd358d
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

Verknüpfte Notizen

Wird geladen…