Methyl 4-aminobenzoate → Rac-4-{[(2r,3r,4r,5s)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl ester

HRID 1807229Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1807229
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:16]2[C:20]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[F:30])([C:21]#[N:22])[CH:19]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[NH:18][CH:17]2[C:36]([OH:38])=O)[CH:12]=[CH:13][C:14]=1[F:15].[NH2:39][C:40]1[CH:49]=[CH:48][C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=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>C(Cl)Cl>[CH3:47][O:46][C:44](=[O:45])[C:43]1[CH:48]=[CH:49][C:40]([NH:39][C:36]([C@H:17]2[C@H:16]([C:11]3[CH:12]=[CH:13][C:14]([F:15])=[C:9]([Cl:8])[CH:10]=3)[C@:20]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[F:30])([C:21]#[N:22])[C@H:19]([CH2:31][C:32]([CH3:35])([CH3:33])[CH3:34])[NH:18]2)=[O:38])=[CH:41][CH:42]=1

Komponenten

6

Edukt 4

HCID 12082Methyl 4-aminobenzoateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86640342rac-(2R,3R,4R,5S)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid

Produkt 1

HCID 59249384Rac-4-{[(2r,3r,4r,5s)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl esterAusbeute 48,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a manner similar to the method described in Examples 1e, rac-(2R,3R,4R,5S)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 69c (0.25 g, 0.43 mmol) was reacted with methyl 4-aminobenzoate (0.12 g, 0.8 mmol), HATU (0.29 g, 0.43 mmol) and iPr2NEt (0.19 mL, 1.1 mmol) in CH2Cl2 at room temperature to give rac-4-{[(2R,3R,4R,5S)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl ester as a white solid (0.125 g, 48%).

Quellen und Nachweise

ORD-Eintrag
ord-f8590adc15b84609aa1515cafc15c5a3
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354444B2

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