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

HRID 1806804Notes

Reaction equation

HRID 1806804 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=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](O)=[O:26])[CH:16]2[C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)=[C:11]([O:37][CH3:38])[CH:10]=1.[CH2:39]([NH2:41])[CH3:40].CN(C([O:49]N1N=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:49][C@H:2]([CH2:3][OH:5])[CH2:40][CH2:39][NH:41][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[O:37][CH3:38])([C:35]#[N:36])[CH:19]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[NH:18]1)=[O:26]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6341EthylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67296949rac-(2S,3R,4R,5S)-4-(4-chloro-2-methoxy-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid

Product 1

HCID 86640329rac-(2S,3R,4R,5S)-4-(4-chloro-2-methoxy-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amideYield 84%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a manner similar to the method described in Examples 42c, 42d, rac-(2S,3R,4R,5S)-4-(4-chloro-2-methoxy-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 61c (0.2 g, 0.35 mmol) was reacted with 2-4S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.15 g, 1.0 mmol), HATU (0.24 g, 0.63 mmol) and iPr2NEt (0.3 mL, 1.7 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-(2S,3R,4R,5S)-4-(4-chloro-2-methoxy-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 (0.15 g, 84%).

Sources & evidence

ORD record
ord-3999598044c34528bbb216949f9f7f86
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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