1-Hydroxybenzotriazole → 2'-Cyano-4'-methyl-5-(pyrrolidine-1-carbonyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)biphenyl-3-carboxamide

HRID 1845198Notes

Reaction equation

HRID 1845198 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[C:10]1[CH:15]=[C:14]([C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])[CH:13]=[C:12]([C:23](O)=[O:24])[CH:11]=1)#[N:2].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[F:57][C:58]([F:68])([F:67])[C:59]1[N:64]=[CH:63][C:62]([CH2:65][NH2:66])=[CH:61][CH:60]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[C:10]1[CH:15]=[C:14]([C:16]([N:18]2[CH2:19][CH2:20][CH2:21][CH2:22]2)=[O:17])[CH:13]=[C:12]([C:23]([NH:66][CH2:65][C:62]2[CH:63]=[N:64][C:59]([C:58]([F:68])([F:57])[F:67])=[CH:60][CH:61]=2)=[O:24])[CH:11]=1)#[N:2]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27377185-(Aminomethyl)-2-(trifluoromethyl)pyridineHCID 581881162'-Cyano-4'-methyl-5-(pyrrolidine-1-carbonyl)biphenyl-3-carboxylic acid

Product 1

HCID 581881742'-Cyano-4'-methyl-5-(pyrrolidine-1-carbonyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)biphenyl-3-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A round-bottom flask was charged with 2′-cyano-4′-methyl-5-(pyrrolidine-1-carbonyl)biphenyl-3-carboxylic acid (50 mg, 0.1 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (52 mg, 0.27 mmol), 1-hydroxybenzotriazole (36 mg, 0.27 mmol), N,N-diisopropylethylamine (35 mg, 0.27 mmol), methylene chloride (4 mL), 4-dimethylaminopyridine (1 mg), and C-(6-trifluoromethyl-pyridin-3-yl)-methylamine (47 mg, 0.27 mmol). The mixture was stirred at room temperature overnight, and then diluted with CH2Cl2, washed with aq. Na2HPO4, brine, and dried over Na2SO4, and concentrated. The residue was purified via preparative HPLC to afford the desired product as a white solid.

Workup

  1. washwashed with aq. Na2HPO4, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified via preparative HPLC

Sources & evidence

ORD record
ord-9158514821af4b0788793178e4ff151f
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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