4-(Trifluoromethyl)benzylamine → HCID 44547646, Verbindung

HRID 1676576Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676576
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:33][C:34]([F:44])([F:43])[C:35]1C=CC(CN)=CC=1.F[P-](F)(F)(F)(F)F.C[N:53](C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)CC)(C)C>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:53][CH2:35][C:34]([F:44])([F:43])[F:33])=[O:28])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

8

Edukt 4

HCID 768044-(Trifluoromethyl)benzylamineHCID 81531DiisopropylethylamineHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 178484293HCID 178484293, Verbindung

Produkt 1

HCID 44547646HCID 44547646, VerbindungAusbeute 57,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A mixture of 0.070 g (0.16 mmole) 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-methoxy-benzoic acid (I-22), 0.027 g (0.19 mmole) of 4-trifluoromethyl-benzylamine, 0.071 g (0.19 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.136 mL (0.78 mmole) of diisopropylethyl amine and 2.0 mL of dimethylformamide was stirred for 18 hours. The mixture was diluted with 10 mL of water plus 2 mL of saturated aqueous sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes-ethyl acetate (gradient, 80:20-0:100) to give 0.049 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-methoxy-N-(2,2,2-trifluoro-ethyl)-benzamide (I-31) as a white solid.

Aufarbeitung

  1. extractionextracted 3 times with 10 mL of ethyl acetate
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with hexanes-ethyl acetate (gradient, 80:20-0:100)

Quellen und Nachweise

ORD-Eintrag
ord-1d00afaf30e14e3ca1793376232b56d6
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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