Diisopropylethylamine → rac-(2R,3S,4R,5S)-5-[2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid [2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-amide

HRID 1807052Notes

Reaction equation

HRID 1807052 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:43])=[C:11]([CH:15]2[C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[CH:18]([CH2:30][C:31]([C:34]3CCOCC=3)([CH3:33])[CH3:32])[NH:17][CH:16]2[C:40]([OH:42])=O)[CH:12]=[CH:13][CH:14]=1.[CH3:44][C:45]1([CH3:53])[O:49][C@@H:48]([CH2:50][CH2:51][NH2:52])[CH2:47][O:46]1.CN(C(ON1N=N[C:64]2[CH:65]=[CH:66][CH:67]=N[C:63]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:78][CH2:79][N:80]([CH:84]([CH3:86])C)[CH:81]([CH3:83])C>C(Cl)Cl>[CH3:44][C:45]1([CH3:53])[O:49][C@@H:48]([CH2:50][CH2:51][NH:52][C:40]([CH:16]2[CH:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=3[F:43])[C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[CH:18]([CH2:30][C:31]([C:34]3[CH2:86][CH2:84][N:80]([CH2:79][C:78]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)[CH2:81][CH:83]=3)([CH3:32])[CH3:33])[NH:17]2)=[O:42])[CH2:47][O:46]1

Participants

6

Reactant 4

HCID 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 86640449rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[2-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-propyl]-pyrrolidine-2-carboxylic acid trifluoroacetic acid

Product 1

HCID 86640444rac-(2R,3S,4R,5S)-5-[2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid [2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Examples 42c, rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[2-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-propyl]-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 129c (0.8 g, 1.2 mmol) was reacted with 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.36 g, 2.5 mmol), HATU (0.84 g, 2.2 mmol) and iPr2NEt (0.64 mL, 3.7 mmol) in CH2Cl2 at room temperature for 20 h to give rac-(2R,3S,4R,5S)-5-[2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid [2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-amide as a off white gum (0.6 g, 74%).

Sources & evidence

ORD record
ord-d60ea702a18441b1ad5fc81a120e0928
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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