Triethylamine → {1-[4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoyl]-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 1676556Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676556
[CH:1]1([N:5]2[CH2:11][C:10]([F:13])([F:12])[C:9](=[O:14])[N:8]([CH3:15])[C:7]3[CH:16]=[N:17][C:18]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=4)=[N:19][C:6]2=3)[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(=[N+](C)C)ON1C2=NC=CC=C2N=N1)C.F[P-](F)(F)(F)(F)F.Cl.[CH:62]1[C:74]2[CH:73]([CH2:75][O:76][C:77](=[O:85])[NH:78][CH:79]3[CH2:84][CH2:83][NH:82][CH2:81][CH2:80]3)[C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[C:66]=2[CH:65]=[CH:64][CH:63]=1>C(OCC)(=O)C.CN(C)C=O>[CH:62]1[C:74]2[CH:73]([CH2:75][O:76][C:77](=[O:85])[NH:78][CH:79]3[CH2:80][CH2:81][N:82]([C:25](=[O:26])[C:24]4[CH:28]=[CH:29][C:21]([NH:20][C:18]5[N:17]=[CH:16][C:7]6[N:8]([CH3:15])[C:9](=[O:14])[C:10]([F:12])([F:13])[CH2:11][N:5]([CH:1]7[CH2:4][CH2:3][CH2:2]7)[C:6]=6[N:19]=5)=[CH:22][CH:23]=4)[CH2:83][CH2:84]3)[C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[C:66]=2[CH:65]=[CH:64][CH:63]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 9886HexafluorophosphateHCID 27562184-(Fmoc-amino)piperidine hydrochlorideHCID 4641409(Dimethylamino)-N,N-dimethyl(3H-(1,2,3)triazolo(4,5-b)pyridin-3-yloxy)methaniminiumHCID 445472064-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid

Produkt 1

HCID 67354975{1-[4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoyl]-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl esterAusbeute 50,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 0.250 g (0.62 mmole) of 4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid (I-11), 0.250 g (2.48 mmole) of triethylamine, 0.319 g (0.74 mmole) of N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-methanaminium, hexafluorophosphate(1-) (1:1) and 5 mL of dimethylformamide was stirred for 15 minutes and then 0.267 g (0.74 mmole) of 4-piperidinyl-carbamic acid 9H-fluoren-9-ylmethyl ester monohydrochloride was added. The mixture was stirred for 3 hours, then taken up in 100 mL of ethyl acetate and washed twice with 100 mL of water and then 100 mL of brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexane-ethyl acetate (gradient 50:50-0:100) to give 0.220 g of {1-[4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoyl]-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester.

Aufarbeitung

  1. stirringThe mixture was stirred for 3 hours
  2. washwashed twice with 100 mL of water
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with hexane-ethyl acetate (gradient 50:50-0:100)

Quellen und Nachweise

ORD-Eintrag
ord-d05314ac5eb644639a00b6003ed67ad8
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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