Sodium Carbonate → 4-[9-cyclopentyl-7,7-difluoro-6-oxo-5-(2,2,2-trifluoro-ethyl)-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 1676684Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676684
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:10](=[O:17])[C:9]([F:19])([F:18])[CH2:8][N:7]([CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[C:6]=2[N:25]=1.[NH2:26][C:27]1[CH:42]=[CH:41][C:30]([C:31]([NH:33][CH:34]2[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]2)=[O:32])=[CH:29][C:28]=1[O:43][CH3:44].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C(O)(C)C>[CH:20]1([N:7]2[CH2:8][C:9]([F:19])([F:18])[C:10](=[O:17])[N:11]([CH2:12][C:13]([F:14])([F:15])[F:16])[C:5]3[CH:4]=[N:3][C:2]([NH:26][C:27]4[CH:42]=[CH:41][C:30]([C:31]([NH:33][CH:34]5[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]5)=[O:32])=[CH:29][C:28]=4[O:43][CH3:44])=[N:25][C:6]2=3)[CH2:24][CH2:23][CH2:22][CH2:21]1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 866375072-Chloro-9-cyclopentyl-7,7-difluoro-5-(2,2,2-trifluoro-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Produkt 1

HCID 580151024-[9-cyclopentyl-7,7-difluoro-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamideAusbeute 47,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 0.10 g (0.26 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-(2,2,2-trifluoro-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-150), 0.072 g (0.27 mmole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.074 g (0.39 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in a pressure tube at 140 degrees overnight. After cooling, dichloromethane and saturated sodium carbonate were added. The mixture was extracted with dichloromethane twice. 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 (100:0-70:30) gave 0.075 g of 4-[9-cyclopentyl-7,7-difluoro-6-oxo-5-(2,2,2-trifluoro-ethyl)-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-150) as a white solid.

Aufarbeitung

  1. temperaturewas heated in a pressure tube at 140 degrees overnight
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted with dichloromethane twice
  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 (100:0-70:30)

Quellen und Nachweise

ORD-Eintrag
ord-d66eaa55d98945eb9abe4018ab0e1685
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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