Diisopropylethylamine → N-[3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-4-methyl-3-([5-(pyrrolidin-1-ylmethyl)pyridin-3-yl]ethynyl}benzamide

HRID 1527849Notes

Reaction equation

HRID 1527849 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:8]=1)#[CH:2].[N:15]1([C:20]2[CH:21]=[C:22]([NH:30][C:31](=[O:40])[C:32]3[CH:37]=[CH:36][C:35]([CH3:38])=[C:34](I)[CH:33]=3)[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=2)[CH:19]=[CH:18][N:17]=[CH:16]1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[N:15]1([C:20]2[CH:21]=[C:22]([NH:30][C:31](=[O:40])[C:32]3[CH:37]=[CH:36][C:35]([CH3:38])=[C:34]([C:2]#[C:1][C:3]4[CH:4]=[N:5][CH:6]=[C:7]([CH2:9][N:10]5[CH2:14][CH2:13][CH2:12][CH2:11]5)[CH:8]=4)[CH:33]=3)[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=2)[CH:19]=[CH:18][N:17]=[CH:16]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 212559433-Ethynyl-5-(pyrrolidin-1-ylmethyl)pyridineHCID 44222638N-(3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide

Product 1

HCID 24873330N-[3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-4-methyl-3-([5-(pyrrolidin-1-ylmethyl)pyridin-3-yl]ethynyl}benzamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-Ethynyl-5-(pyrrolidin-1-ylmethyl)pyridine (0.52 mmol), 0.245 g (0.52 mmol) of N-(3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide (as prepared above), 0.030 g (0.026 mmol) of Pd(PPh3)4, 0.007 g (0.039 mmol) of CuI, and 0.14 mL (0.78 mmol) of diisopropylethylamine in 3.0 mL of DMF is stirred at ambient temperature overnight under an atmosphere of N2. The reaction mixture is concentrated and the crude product is purified by silica gel flash chromatography (eluted with 10% EtOAc/hexanes, then 100% EtOAc, then 10% MeOH/EtOAc) to provide the title product.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. customthe crude product is purified by silica gel flash chromatography (
  3. washeluted with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-e4798a94ebe54fff9e930304ca2f6e6f
Source dataset
uspto-grants-2015_07
Patent number
US09090561B2

Reaction notes

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