Dicyclohexylcarbodiimide → 3-(4-(4-(3-(1-Triphenylmethyl-4-imidazolyl)propanoyl)-piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one

HRID 1167444Notes

Reaction equation

HRID 1167444 reaction equation
[C:1]1([C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15](O)=[O:16])[N:10]=[CH:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.Cl.Cl.[N:57]1([C:63]2[CH:68]=[CH:67][C:66]([N:69]3[CH2:73][C@H:72]([CH2:74][O:75][C:76]4[CH:80]=[CH:79][O:78][N:77]=4)[O:71][C:70]3=[O:81])=[CH:65][C:64]=2[F:82])[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1.C(N(CC)C(C)C)(C)C>ClCCl>[C:24]1([C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([N:60]3[CH2:59][CH2:58][N:57]([C:63]4[CH:68]=[CH:67][C:66]([N:69]5[CH2:73][C@H:72]([CH2:74][O:75][C:76]6[CH:80]=[CH:79][O:78][N:77]=6)[O:71][C:70]5=[O:81])=[CH:65][C:64]=4[F:82])[CH2:62][CH2:61]3)=[O:16])[N:10]=[CH:9]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 74084421-(Triphenylmethyl)-1H-imidazole-4-propanoic acidHCID 69980303HCID 69980303, compound

Product 1

HCID 699799123-(4-(4-(3-(1-Triphenylmethyl-4-imidazolyl)propanoyl)-piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-oneYield 63.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-(1-Triphenylmethyl-4-imidazolyl)propionic acid (420 mg, 1.1 mmol) was suspended in dichloromethane (10 ml) under nitrogen, and treated successively with dicyclohexylcarbodiimide (227 mg, 1.1 mmol) and 1-hydroxybenzotriazole (149 mg, 1.1 mmol), then stirred at ambient temperature for 30 minutes. To it was added a solution of 3-(4-(piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one dihydrochloride (435 mg, 1 mmol) and N,N-diisopropylethylamine (258 mg, 2 mmol) in dichloromethane (5 ml). The mixture was stirred for 18 hours at the same temperature, solid filtered off, and the organic phase purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 15% MeOH in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (460 mg).

Workup

  1. stirringThe mixture was stirred for 18 hours at the same temperature, solid
  2. filtrationfiltered off
  3. customthe organic phase purified by chromatography on a 20 g silica Mega Bond Elut® column
  4. washeluting with a gradient
  5. temperatureincreasing in polarity from 0 to 15% MeOH in dichloromethane
  6. customevaporated

Sources & evidence

ORD record
ord-7d8f8c6bc6074053b9263a9b09300f61
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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