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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → Ethyl (2S)-3-[3-({(3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorophenyl]-2-methylpropanoate

HRID 626427
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 626427
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([OH:21])=O)[C@H:13]([C:15]([F:18])([F:17])[F:16])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[F:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([NH:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[F:29])=[O:21])[C@H:13]([C:15]([F:16])([F:17])[F:18])[CH3:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
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Komponenten

7

Edukt 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58288322(+)-ethyl (2S)-3-(3-amino-4-fluorophenyl)-2-methylpropanoateHCID 118106631(3R)-N-[(Benzyloxy)carbonyl]-4,4,4-trifluorovaline

Produkt 1

HCID 131735217Ethyl (2S)-3-[3-({(3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorophenyl]-2-methylpropanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1049PyridineLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

0.87 g (2.85 mmol) of (3R)—N-[(benzyloxy)carbonyl]-4,4,4-trifluorovaline (diastereomer mixture) and 0.77 g (3.42 mmol) of (+)-ethyl (2S)-3-(3-amino-4-fluorophenyl)-2-methylpropanoate were dissolved in a mixture of 5 ml of DMF and 2.5 ml of pyridine, and 1.41 g (3.71 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight and then diluted with ethyl acetate. The mixture was washed successively with 1 N hydrochloric acid, sat. sodium bicarbonate solution and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1). This gave 1.27 g of the target product (87.2% of theory, diastereomer ratio about 4.8:1).

Aufarbeitung

  1. additionwere added at RT
  2. washThe mixture was washed successively with 1 N hydrochloric acid, sat. sodium bicarbonate solution and sat. sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1)

Quellen und Nachweise

ORD-Eintrag
ord-8f7399f3a6444e13a02dbdc8dba35764
Quelldatensatz
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09309198B2

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