4-Methylmorpholine → (S)-N-(1-cyanocyclopropyl)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanamide

HRID 384734Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 384734
[F:1][C:2]([F:28])([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][C@H:4]([NH:8][C@@H:9]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:10]([F:13])([F:12])[F:11])[C:5]([OH:7])=O.C(O)(=O)CCCC.Cl.[NH2:37][C:38]1([C:41]#[N:42])[CH2:40][CH2:39]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[C:41]([C:38]1([NH:37][C:5](=[O:7])[C@@H:4]([NH:8][C@@H:9]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:10]([F:11])([F:13])[F:12])[CH2:3][C:2]([F:28])([F:1])[CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:40][CH2:39]1)#[N:42]

Komponenten

8

Edukt 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 86625058pentanoic acid (S)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanoic acid

Produkt 1

HCID 24764492(S)-N-(1-cyanocyclopropyl)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of the above pentanoic acid (S)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanoic acid, (1 mmol), 1-aminocyclopropanecarbonitrile hydrochloride (1.2 mmol), HATU (1.2 mmol) and NMM (4.0 mmol), in DMF, was stirred at RT for 2 hr. Saturated ammonium chloride and ethyl acetate were then added, and the reaction was stirred an additional 20 min at RT, after which product was extracted with ethyl acetate, purified with flash column (30-35% ethyl acetate-hexane), and crystallized with DCM-hexane to give (S)—N-(1-cyanocyclopropyl)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanamide as a white crystal. 1H-NMR (CDCl3) δ 8.9 (1H), 7.2-7.5 (9H, m), 4.33 (1H, m), 3.2-3.5 (3H), 2.0-2.6 (2H), 1.6-1.8 (2H), 0.75 (1H), 0.58 (1H). 19F-NMR (CDCl3) δ−113 ppm. LC/EIMS (m/z): 470 (M+Na)+.

Aufarbeitung

  1. extractionafter which product was extracted with ethyl acetate
  2. custompurified with flash column (30-35% ethyl acetate-hexane)
  3. customcrystallized with DCM-hexane

Quellen und Nachweise

ORD-Eintrag
ord-4d45cfde9bb04ac2a0061029a8a1155b
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367732B2

Notizen zur Reaktion

Wird geladen…