1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-[1-(4-bromophenyl)-1-methylethyl]-1-[(15-methyl-8-nitrotetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaen-15-yl)carbonyl]-1H-1,2,4-triazol-5-amine

HRID 900828Notes

Reaction equation

HRID 900828 reaction equation
[CH3:1][C:2]1([C:21]([OH:23])=O)[CH2:17][C:10]2([N+:18]([O-:20])=[O:19])[C:11]3[C:16]([CH:3]1[C:4]1[C:9]2=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH:15][CH:14]=[CH:13][CH:12]=3.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.CCN=C=NCCCN(C)C.[Br:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]([C:64]2[NH:68][N:67]=[C:66]([NH2:69])[N:65]=2)([CH3:63])[CH3:62])=[CH:57][CH:56]=1>C(#N)C>[Br:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]([C:64]2[N:65]=[C:66]([NH2:69])[N:67]([C:21]([C:2]3([CH3:1])[CH2:17][C:10]4([N+:18]([O-:20])=[O:19])[C:9]5[C:4]([CH:3]3[C:16]3[C:11]4=[CH:12][CH:13]=[CH:14][CH:15]=3)=[CH:5][CH:6]=[CH:7][CH:8]=5)=[O:23])[N:68]=2)([CH3:63])[CH3:62])=[CH:57][CH:56]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 586702735-[1-(4-bromophenyl)-1-methylethyl]-1H-1,2,4-triazol-3-amineHCID 596985749-Nitro-9,10-dihydro-11-methyl-9,10-ethanoanthracene-11-carboxylic acid

Product 1

HCID 586703343-[1-(4-bromophenyl)-1-methylethyl]-1-[(15-methyl-8-nitrotetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaen-15-yl)carbonyl]-1H-1,2,4-triazol-5-amineYield 93%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 15-methyl-8-nitrotetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaene-15-carboxylic acid (31 mg, 0.10 mmol, prepared according to WO04009017), 1-hydroxybenzotriazole (20 mg, 0.15 mmol), and N-ethyl-N,N-diisopropylamine (0.15 mL) in anhydrous acetonitrile (1.5 mL) was added EDCI (39 mg, 0.2 mmol) at RT under argon. After the mixture was stirred at RT for 5 min, 5-[1-(4-bromophenyl)-1-methylethyl]-1H-1,2,4-triazol-3-amine (28 mg, 0.1 mmol) was added. The reaction mixture was stirred at RT for 2 h and at 80° C. for 1 h. After the solvents were removed, the residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate solution. The aqueous solution was extracted with methylene chloride. The combined organic solutions were dried (Na2SO4), concentrated and purified by silica gel chromatography to give 53 mg (93% yield) of the title compound as a white solid which was used as such for the subsequent step without further purification.

Workup

  1. stirringThe reaction mixture was stirred at RT for 2 h and at 80° C. for 1 h
  2. customAfter the solvents were removed
  3. customthe residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate solution
  4. extractionThe aqueous solution was extracted with methylene chloride
  5. dry with materialThe combined organic solutions were dried (Na2SO4)
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-62082d91f66a4cbe84672052c5a41229
Source dataset
uspto-grants-2008_04
Patent number
US07361654B2

Reaction notes

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