1,2-Dimethoxyethane → 5-((4-(Benzyloxy)benzyl)(4H-1,2,4-triazol-4-yl)amino)biphenyl-2,4'-dicarbonitrile

HRID 82781Notes

Reaction equation

HRID 82781 reaction equation
[CH2:1]([O:8][C:9]1[CH:30]=[CH:29][C:12]([CH2:13][N:14]([N:24]2[CH:28]=[N:27][N:26]=[CH:25]2)[C:15]2[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[C:17](Br)[CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:31]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)#[N:32].C(COC)OC.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:30]=[CH:29][C:12]([CH2:13][N:14]([N:24]2[CH:28]=[N:27][N:26]=[CH:25]2)[C:15]2[CH:16]=[C:17]([C:36]3[CH:37]=[CH:38][C:33]([C:31]#[N:32])=[CH:34][CH:35]=3)[C:18]([C:19]#[N:20])=[CH:21][CH:22]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 682284294-((4-(benzyloxy)benzyl)(4H-1,2,4-triazol-4-yl)amino)-2-bromobenzonitrile

Product 1

HCID 682277955-((4-(Benzyloxy)benzyl)(4H-1,2,4-triazol-4-yl)amino)biphenyl-2,4'-dicarbonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-((4-(benzyloxy)benzyl)(4H-1,2,4-triazol-4-yl)amino)-2-bromobenzonitrile (CAB05114, 0.460 g, 1.0 mmol), 4-cyanophenylboronic acid (0.184 g, 1.25 mmol), dimethoxyethane (20 mL) and 2M Na2CO3 (20 mL) was heated to reflux before Pd2(dba)3 (0.05 g) was added and heating was continued for 5 hours. After cooling to room temperature EtOAc (50 mL) was added to and the mixture was filtered (celite). The organic layer was separated, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography [SiO2, CHCl3/acetone (2:1)] to afford CAB06075 (4.03 g, 71%) as a white solid. Mp. 234-237-113° C.; 1H NMR (400 MHz, DMSO-d6) δ 5.02 (s, 4H), 6.72 (dd, J=8.6, 2.7 Hz, 1H), 6.91 (d, J=2.7 Hz, 1H), 6.95 (AA′BB′, 2H), 7.21 (AA′BB′, 2H), 7.30-7.45 (m, 5H), 7.75 (AA′BB′, 2H), 7.90 (d, J=8.6 Hz, 1H), 8.02 (AA′BB′, 2H), 8.75 (s, 2H); 13C NMR (100.6 MHz, DMSO-d6) δ 56.5, 69.2, 101.7, 111.7, 113.4, 113.7, 114.1, 114.8, 118.3, 118.4, 126.4, 127.8, 127.9, 128.4, 129.7, 130.0, 130.1, 132.7, 135.6, 136.9, 142.3, 143.3, 144.5, 145.9, 151.5, 158.2; LRMS (ES+): m/z 4833 (100%, [M+H]+); HRMS (ES+) calcd for C30H23N6O [M+H]+: 483.1928. found 483.1918.

Workup

  1. temperaturewas heated
  2. additionwas added
  3. temperatureheating
  4. additionwas added to and the mixture
  5. filtrationwas filtered (celite)
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography [SiO2, CHCl3/acetone (2:1)]
  10. customto afford CAB06075 (4.03 g, 71%) as a white solid
  11. custom237-113° C.

Sources & evidence

ORD record
ord-7056dbfbabc54ff3870d7f7d322bf932
Source dataset
uspto-grants-2014_09
Patent number
US08846737B2

Reaction notes

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