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-(1-(2-hydroxyethyl)piperidin-4-yl)-3-methoxybenzamide

HRID 1676798Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676798
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:53]=[CH:52][C:39]([C:40]([NH:42][CH:43]2[CH2:48][CH2:47][N:46]([CH2:49][CH2:50][OH:51])[CH2:45][CH2:44]2)=[O:41])=[CH:38][C:37]=1[O:54][CH3:55]>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:53]=[CH:52][C:39]([C:40]([NH:42][CH:43]5[CH2:44][CH2:45][N:46]([CH2:49][CH2:50][OH:51])[CH2:47][CH2:48]5)=[O:41])=[CH:38][C:37]=4[O:54][CH3:55])=[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 579555542-Chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneHCID 580150034-Amino-N-[1-(2-hydroxyethyl)-4-piperidinyl]-3-methoxybenzamide

Produkt 1

HCID 252540014-(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-(1-(2-hydroxyethyl)piperidin-4-yl)-3-methoxybenzamideAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

A mixture of 0.112 g (0.34 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), 0.097 g (0.51 mmole) of toluenesulfonic acid monohydrate, 0.10 g (0.34 mmole) of 4-amino-N-[1-(2-hydroxy-ethyl)-piperidin-4-yl]-3-methoxy-benzamide and 1 mL of isopropanol was heated in a sealed vessel at 170 degrees in a microwave reactor for 2 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 by preparative thin layer chromatography, eluting with dichloromethane-methanol (90:10) to give 0.040 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-[1-(2-hydroxy-ethyl)-piperidin-4-yl]-3-methoxy-benzamide (I-267).

Aufarbeitung

  1. temperaturewas heated in a sealed vessel at 170 degrees in a microwave reactor for 2 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. washeluting with dichloromethane-methanol (90:10)

Quellen und Nachweise

ORD-Eintrag
ord-55b4acfef06e424dba7fb72187f1c3d4
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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