1-Hydroxybenzotriazole → HCID 86587638, compound

HRID 1782728Notes

Reaction equation

HRID 1782728 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:24]=[C:25]([Br:28])[C:26]=1[OH:27])[CH2:5][C@H:6]([C:21]([OH:23])=O)[NH:7][C:8]([NH:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)=[O:9].[CH3:29]CN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[NH2:70][C@H:71]([C:84]([O:86]C)=[O:85])[CH2:72][CH2:73][CH2:74][CH2:75][NH:76][C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78]>CN(C)C=O>[CH3:29][N:70]([C:21](=[O:23])[C@@H:6]([CH2:5][C:4]1[CH:24]=[C:25]([Br:28])[C:26]([OH:27])=[C:2]([Br:1])[CH:3]=1)[NH:7][C:8]([NH:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)=[O:9])[C@H:71]([C:84]([OH:86])=[O:85])[CH2:72][CH2:73][CH2:74][CH2:75][NH:76][C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7018776(S)-Methyl 2-amino-6-((tert-butoxycarbonyl)amino)hexanoateHCID 53706294HCID 53706294, compound

Product 1

HCID 86587638HCID 86587638, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 10 g (19.4 mmol) of 3,5-dibromo-N-[[[2-(3-methoxyphenyl)ethyl]amino]carbonyl]-D-tyrosine, 2.6 g (20 mmol) of DIEA, 6.4 g (20 mmol) of TBTU, 2.64 g (19.5 mmol) of HOBt and 200 ml of dimethylformamide was added dropwise, with stirring, a solution of 5.04 g (19.4 mmol) of H-Lys(Boc)-OMe in 50 ml of dimethylformamide and the mixture was stirred over-night at room temperature. The reaction mixture was evaporated down in vacuo and the residue was taken up in 250 ml of ethyl acetate. The ethyl acetate phase was then washed twice with 100 ml of saturated aqueous sodium hydrogen carbonate solution, once with 100 ml of 20% aqueous citric acid solution and finally once with 100 ml of saturated aqueous saline solution. The organic phase was dried with sodium sulphate, evaporated down in vacuo and the residue was purified by column chromatography (MN-silica gel 60, Macherey-Nagel, 70-230 mesh ASTM, eluant: ethyl acetate/petroleum ether=2/1 (v/v)). After removal of the solvent in vacuo the residue was triturated with ether, the amorphous solid obtained (9.5 g; 660 of theory) was suction filtered and dried.

Workup

  1. additionwas added dropwise
  2. customThe reaction mixture was evaporated down in vacuo
  3. washThe ethyl acetate phase was then washed twice with 100 ml of saturated aqueous sodium hydrogen carbonate solution, once with 100 ml of 20% aqueous citric acid solution and finally once with 100 ml of saturated aqueous saline solution
  4. dry with materialThe organic phase was dried with sodium sulphate
  5. customevaporated down in vacuo
  6. customthe residue was purified by column chromatography (MN-silica gel 60, Macherey-Nagel, 70-230 mesh ASTM, eluant: ethyl acetate/petroleum ether=2/1 (v/v))
  7. customAfter removal of the solvent in vacuo the residue
  8. customwas triturated with ether
  9. customthe amorphous solid obtained (9.5 g; 660 of theory)
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-19efd7b90aef4a038c0b9964b6ddaf4d
Source dataset
uspto-grants-2009_03
Patent number
US07498325B2

Reaction notes

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