Trifluoroacetic acid → 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)-3-methyl-N-piperidin-4-yl-benzamide

HRID 1676724Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676724
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:44])[C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]3[N:24]=[CH:25][C:26]4[N:32]([CH3:33])[C:31](=[O:34])[C:30]([F:36])([F:35])[CH2:29][N:28]([CH:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[C:27]=4[N:42]=3)=[C:18]([CH3:43])[CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH:37]1([N:28]2[CH2:29][C:30]([F:35])([F:36])[C:31](=[O:34])[N:32]([CH3:33])[C:26]3[CH:25]=[N:24][C:23]([NH:22][C:19]4[CH:20]=[CH:21][C:16]([C:15]([NH:14][CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)=[O:44])=[CH:17][C:18]=4[CH3:43])=[N:42][C:27]2=3)[CH2:41][CH2:40][CH2:39][CH2:38]1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 580150614-[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)-3-methyl-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 580151584-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methyl-N-piperidin-4-yl-benzamideAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 0.071 g (0.115 mmole) of 4-[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)-3-methyl-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester (I-191) in 4 mL of dichloromethane was stirred with 2 mL of trifluoroacetic acid for 2 hours and concentrated under reduced pressure. The residue was dissolved in 80 mL of dichloromethane, washed with 15 mL of sodium carbonate solution, twice with 15 mL of brine and concentrated under reduced pressure. The residue was purified by reverse phase silica gel chromatography, eluting with water-acetonitrile (gradient, 90:10-0:100) to give 0.0549 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)-3-methyl-N-piperidin-4-yl-benzamide (I-192) as a white solid.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 80 mL of dichloromethane
  3. washwashed with 15 mL of sodium carbonate solution, twice with 15 mL of brine
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase silica gel chromatography
  6. washeluting with water-acetonitrile (gradient, 90:10-0:100)

Quellen und Nachweise

ORD-Eintrag
ord-03e16ceb6706423b9671c9cf1140bf78
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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