Dimethylformamide → HCID 53357227, compound

HRID 1807269Notes

Reaction equation

HRID 1807269 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.CCN([CH:38]([CH3:40])C)C(C)C.[Cl-].C[NH3+].[CH:44]1[CH:45]=[CH:46][C:47]2[N:52](O)N=[N:50][C:48]=2[CH:49]=1.CN([C:57]([O:61]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C)C=[O:81]>>[CH2:38]([O:81][C:57](=[O:61])[C:49]1[CH:44]=[CH:45][C:46]([CH2:47][NH:52][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:25])([CH3:26])[CH3:27])[NH:10]2)=[O:29])=[N:50][CH:48]=1)[CH3:40]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 11637Methanamine, hydrochloride (1:1)HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666882513-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

Product 1

HCID 53357227HCID 53357227, compound

Procedure

In a manner similar to the method described in Example 379, chiral 2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (60.9 mg, 0.130 mmol) in N,N-dimethyl formamide (5 mL) were reacted with DIPEA (134 mg, 1.03 mmol), 5-(ethoxycarbonyl)pyridin-2-yl)methanaminium chloride (68.5 mg, 0.316 mmol, Chem-Impex), HOBt (34.0 mg, 0.252 mmol) and HBTU (93.5 mg, 0.247 mmol) at room temperature to give chiral 6-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-nicotinic acid ethyl ester as a white solid, (81.3 mg, 99%). HRMS (ES+) m/z Calcd C32H32Cl2F2N4O3+H [(M+H): 629.1893. Found: 629.1896.

Sources & evidence

ORD record
ord-298d4b7f48d148819fa9d51f527565fb
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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