1-Hydroxybenzotriazole → 1,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methyl{[4-(2-pyridinyl)phenyl]carbonyl}amino)phenyl]methyl}-1-piperazinecarboxylate

HRID 534797Notes

Reaction equation

HRID 534797 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=1.C(N=C=NC1CCCCC1)C1C=CC=CC=1.ON1C2C=CC=CC=2N=N1.[CH3:42][C@H:43]1[CH2:48][N:47]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([NH:56][CH3:57])=[CH:52][CH:51]=2)[CH2:46][CH2:45][N:44]1[C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59]>CN(C=O)C.C(Cl)Cl>[CH3:42][C@H:43]1[CH2:48][N:47]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([N:56]([CH3:57])[C:11]([C:10]3[CH:9]=[CH:8][C:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[CH:15][CH:14]=3)=[O:13])=[CH:52][CH:51]=2)[CH2:46][CH2:45][N:44]1[C:58]([O:60][C:61]([CH3:62])([CH3:64])[CH3:63])=[O:59]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 8216924-(2-Pyridyl)Benzoic AcidHCID 5067457N-benzyl-N'-cyclohexylcarbodiimideHCID 592621311,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate

Product 1

HCID 592622261,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methyl{[4-(2-pyridinyl)phenyl]carbonyl}amino)phenyl]methyl}-1-piperazinecarboxylateYield 35.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To 4-(2-pyridinyl)benzoic acid (0.0624 g, 0.313 mmol) in DMF (3 mL) was added N-benzyl-N′-cyclohexylcarbodiimide resin (0.294 g, 1.6 mmol/g, 0.47 mmol), 1-hydroxybenzotriazole (0.064 g, 0.47 mmol) and DCM (1 mL) and the mixture was shaken for 30 minutes. 1,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazine-carboxylate (D3) (100 mg, 0.313 mmol), DMF (3 mL) and DCM (1 mL) were then added and the mixture was shaken for ˜2 days at room temperature The reaction mixture was filtered to remove the resin which was then washed with further DMF/DCM (3:1). The filtrate was concentrated to give the crude product which was purified by column chromatography. Elution with an ether/pentane gradient yielded the title compound (0.055 g). MS (ES): MH+ 501.2.

Workup

  1. stirringthe mixture was shaken for ˜2 days at room temperature The reaction mixture
  2. filtrationwas filtered
  3. customto remove the resin which
  4. washwas then washed with further DMF/DCM (3:1)
  5. concentrationThe filtrate was concentrated
  6. customto give the crude product which
  7. customwas purified by column chromatography
  8. washElution with an ether/pentane gradient

Sources & evidence

ORD record
ord-33bbbc88b864480384c93efe08ecad28
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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