(2S,4R)-4-(2-chloro-4-fluorophenylthio)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide → ethyl 4-(2-((2S,4R)-4-(2-chloro-4-fluorophenylthio)-2-(1-cyanocyclopropylcarbamoyl)pyrrolidine-1-carbonyl)azetidin-1-yl)piperidine-1-carboxylate

HRID 2403184Notes

Reaction equation

HRID 2403184 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9][C@H:10]1[CH2:14][NH:13][C@H:12]([C:15]([NH:17][C:18]2([C:21]#[N:22])[CH2:20][CH2:19]2)=[O:16])[CH2:11]1.[CH2:23]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([N:34]2[CH2:37][CH2:36][CH:35]2[C:38]([O-])=[O:39])[CH2:30][CH2:29]1)=[O:27])[CH3:24].[Li+]>>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9][C@H:10]1[CH2:14][N:13]([C:38]([CH:35]2[CH2:36][CH2:37][N:34]2[CH:31]2[CH2:30][CH2:29][N:28]([C:26]([O:25][CH2:23][CH3:24])=[O:27])[CH2:33][CH2:32]2)=[O:39])[C@H:12]([C:15](=[O:16])[NH:17][C:18]2([C:21]#[N:22])[CH2:20][CH2:19]2)[CH2:11]1

Participants

3

Reactant 2

HCID 86692743(2S,4R)-4-(2-chloro-4-fluorophenylthio)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamideHCID 86692776Lithium 1-(1-(ethoxycarbonyl)piperidin-4-yl)azetidine-2-carboxylate

Product 1

HCID 71712042ethyl 4-(2-((2S,4R)-4-(2-chloro-4-fluorophenylthio)-2-(1-cyanocyclopropylcarbamoyl)pyrrolidine-1-carbonyl)azetidin-1-yl)piperidine-1-carboxylate

Procedure

The reaction of (2S,4R)-4-(2-chloro-4-fluorophenylthio)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 12A and lithium 1-(1-(ethoxycarbonyl)piperidin-4-yl)azetidine-2-carboxylate 20J carried out according to the general procedure L yielded ethyl 4-(2-((2S,4R)-4-(2-chloro-4-fluorophenylthio)-2-(1-cyanocyclopropylcarbamoyl)pyrrolidine-1-carbonyl)azetidin-1-yl)piperidine-1-carboxylate 1:1 epimers as a white solid (82%). MS ISP (m/e): 578.3/580.4 (100/38) [(M+H)]]+.

Sources & evidence

ORD record
ord-314dd4742bc54156b45129c18063e595
Source dataset
uspto-grants-2014_08
Patent number
US08802665B2

Reaction notes

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