Hydrochloric Acid → rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide

HRID 1806816Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1806816
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([C:35]#[N:36])[CH:19]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[NH:18][CH:17]([C:25]([OH:27])=O)[CH:16]2[C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)=[C:11]([F:37])[CH:10]=1.CC1(C)[O:43][C@@H:42]([CH2:44][CH2:45][NH2:46])[CH2:41][O:40]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.O1CCCC1>[OH:43][C@H:42]([CH2:41][OH:40])[CH2:44][CH2:45][NH:46][C:25]([CH:17]1[CH:16]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)[C:15]([C:12]2[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][C:11]=2[F:37])([C:35]#[N:36])[CH:19]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[NH:18]1)=[O:27]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 282937772-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethan-1-amineHCID 86640334rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid

Produkt 1

HCID 86640335rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amideAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

In a manner similar to the method described in Examples 42c, 42d, rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 64c (0.46 g, 0.83 mmol) was reacted with 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.36 g, 2.5 mmol), HATU (0.57 g, 1.5 mmol) and iPr2NEt (0.72 mL, 4.2 mmol) in CH2Cl2 at room temperature for 20 h, then reacted with aqueous HCl solution in tetrahydrofuran at room temperature for 2 h to give rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (0.21 g, 48%).

Quellen und Nachweise

ORD-Eintrag
ord-02f65191d70e45d2834c9447f2124806
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354444B2

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