Dicyclohexylcarbodiimide → 1H-Benzotriazol-1-yl 4-[[(1,1-dimethylethoxy)carbonyl]amino]-1-methyl-1H-imidazole-2-carboxylate

HRID 2289209Notes

Reaction equation

HRID 2289209 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1C=[C:11]([C:15]([OH:17])=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:19]1[C:27]2[N:26]=[N:25][NH:24][C:23]=2[CH:22]=[CH:21][CH:20]=1.C1CCC([N:34]=C=NC2CCCCC2)CC1>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[N:34]=[C:11]([C:15]([O:17][N:26]2[C:27]3[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=3[N:24]=[N:25]2)=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 27356364-[(tert-Butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 234463961H-Benzotriazol-1-yl 4-[[(1,1-dimethylethoxy)carbonyl]amino]-1-methyl-1H-imidazole-2-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The Boc-pyrrole-acid 8 (31 g, 129 mmol) was dissolved in 500 ml DMF and hydroxybenzotriazole (17.4 g, 129 mmol) was added followed by DCC (34 g, 129 mmol). The reaction was allowed to stir for 24 hours and then filtered dropwise into a well stirred solution of 5 liters of water (0° C.). The precipitate was allowed to sit for 15 minutes at 0° C. and then collected by filtration. The wet cake was dissolved in 500 ml of dichloromethane, washed with 200 ml brine, and added slowly to a stirred solution of petroleum ether at -20° C. After 4 hours at -20° C. the precipitate was collected by vacuum filtration and dried in vacuo to give (39 g, 85% yield) of a finely divided white powder. (A yellowish impurity may be observed, which can be removed by flash chromatography (acetone:dichloromethane), followed by precipitation in petroleum ether). TLC (7:2 benzene/ethyl acetate v/v) Rf 0.6; 1H NMR (DMSO-d6) δ 9.43 (s, 1H), 8.12 (d, 1H, J=8.4Hz), 7.80 (d, 1H, J=8.2 Hz), 7.64 (t, 1H, J=7.0 Hz), 7.51 (m, 2H), 7.18 (s, 1H), 3.83 (s, 3H), 1.45 (s, 9H); 13C NMR (DMSO-d6) δ 156.5, 153.3, 143.2, 129.6, 129.2, 125.7, 125.2, 124.6, 120.3, 112.8, 110.3, 109.8, 79.5, 36.8, 28.6.

Workup

  1. filtrationfiltered dropwise into a well
  2. stirringstirred solution of 5 liters of water (0° C.)
  3. waitto sit for 15 minutes at 0° C.
  4. filtrationcollected by filtration
  5. dissolutionThe wet cake was dissolved in 500 ml of dichloromethane
  6. washwashed with 200 ml brine
  7. additionadded slowly to a stirred solution of petroleum ether at -20° C
  8. filtrationAfter 4 hours at -20° C. the precipitate was collected by vacuum filtration
  9. customdried in vacuo
  10. customto give (39 g, 85% yield) of a finely divided white powder
  11. customwhich can be removed by flash chromatography (acetone:dichloromethane)
  12. customfollowed by precipitation in petroleum ether)

Sources & evidence

ORD record
ord-c7da060365934c1991c549358cef50d8
Source dataset
uspto-grants-2000_07
Patent number
US06090947

Reaction notes

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