N,N'-Dimethylethylenediamine → HCID 66710589, compound

HRID 1777490Notes

Reaction equation

HRID 1777490 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[N:17][C:18](Br)=[CH:19][CH:20]=3)=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[C:24]([C:26]1[CH:41]=[CH:40][C:29]([CH2:30][N:31]2[CH2:36][CH2:35][CH:34]([C:37]([NH2:39])=[O:38])[CH2:33][CH2:32]2)=[CH:28][CH:27]=1)#[N:25].CNCCNC.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.C1(C)C=CC=CC=1>[C:24]([C:26]1[CH:27]=[CH:28][C:29]([CH2:30][N:31]2[CH2:32][CH2:33][CH:34]([C:37]([NH:39][C:18]3[N:17]=[CH:16][C:15]([C:13]([N:10]4[CH2:11][CH2:12][N:7]([CH2:6][C:5]5[CH:22]=[CH:23][C:2]([F:1])=[CH:3][CH:4]=5)[CH2:8][CH2:9]4)=[O:14])=[CH:20][CH:19]=3)=[O:38])[CH2:35][CH2:36]2)=[CH:40][CH:41]=1)#[N:25]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 17221193HCID 17221193, compoundHCID 58073332HCID 58073332, compound

Product 1

HCID 66710589HCID 66710589, compoundYield 117.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (4-(4-fluorobenzyl)piperazin-1-yl)(6-bromopyridin-3-yl)methanone (0.040 g, 0.11 mmol, 1.0 eq), 1-(4-cyanobenzyl)piperidine-4-carboxamide (0.028 g, 0.12, 1.1 eq), and N,N′-dimethylethylenediamine (0.012 mL, 0.11 mmol, 1.0 eq) was added anhydrous toluene (1.0 mL). This mixture was purged with argon for 5 minutes and copper(I)iodide (0.011 g, 0.058 mmol, 0.5 eq) and potassium carbonate (0.044 g, 0.23 mmol, 2.1 eq) were added. The reaction mixture was heated at 100° C. for 4.5 hours and then absorbed on silica gel. Purification by column chromatography (silica, 0-*5% MeOH—CH2Cl2) yielded a green solid (0.070 g). Further purification using preparative TLC (silica, 4% MeOH— CH2Cl2) provided Compound 46 as a white solid (0.040 g, 67%). 1H nmr (D6-DMSO) δ 10.64 (1H, s), 8.32 (1H, s), 8.10 (1H, d, J 8.5 Hz), 7.81-7.74 (3H, m), 7.53-7.46 (2H, m), 7.31 (2H, t, J 8.0 Hz), 7.12 (2H, t, J 9.0 Hz), 3.64-3.36 (9H, m), 2.79 (2H, m), 2.35 (m, 4H), 1.99-1.87 (2H, m), 1.79-1.54 (4H, m); m/z: 542 [M+H]+. More information about this type of coupling is provided in Wrona, Iwona E.; Gozman, Alexander; Taldone, Tony; Chiosis, Gabriela; Panek, James S. Journal of Organic Chemistry (2010), 75(9), 2820-2835.

Workup

  1. customThis mixture was purged with argon for 5 minutes
  2. customabsorbed on silica gel
  3. customPurification by column chromatography (silica, 0-*5% MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-1480ea8672904249aaf2b54f86ba8b29
Source dataset
uspto-grants-2016_02
Patent number
US09266856B2

Reaction notes

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