2-Dimethylaminopyridine → HCID 75632056, compound

HRID 909102Notes

Reaction equation

HRID 909102 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[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])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.CN(C1C=CC=CN=1)C.[Cl:47][C:48]1[CH:56]=[CH:55][C:51]([C:52](Cl)=[O:53])=[CH:50][N:49]=1>C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[C:3]([F:28])=[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]([CH3:25])([CH3:27])[CH3:26])[CH2:10][N:9]2[C:52]([C:51]2[CH:50]=[N:49][C:48]([Cl:47])=[CH:56][CH:55]=2)=[O:53])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 27821656-Chloronicotinoyl ChlorideHCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

Product 1

HCID 75632056HCID 75632056, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (53 mg, 0.125 mmol), diisopropylethylamine (64.7 mg, 0.50 mmol), dimethylaminopyridine (3 mg, 0.024 mmol, Aldrich) in CH2Cl2 (6 mL) and 6-chloro-nicotinoyl chloride (41.0 mg, 0.232 mmol, Aldrich) was stirred at room temp. for 2 hrs before diluted with EtOAc, washed with aqueous Na2CO3, brine, and concentrated. The residue was purified by flash column to give rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-1-(6-chloro-pyridine-3-carbonyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (58.3 mg, 83%) as a white solid. HRMS (ES+) m/z Calcd for C28H24Cl3F2N3O+H [(M+H)+]: 562.1026; Found: 562.1026

Workup

  1. washwashed with aqueous Na2CO3, brine
  2. concentrationconcentrated
  3. customThe residue was purified by flash column

Sources & evidence

ORD record
ord-ba7b6be0f0774163afb4f0f41c029f0d
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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