Diisopropylethylamine → HCID 67005749, compound

HRID 563142Notes

Reaction equation

HRID 563142 reaction equation
[CH2:1]([C:6]1[CH:38]=[CH:37][C:9]([CH2:10][N:11]([C:23](=[O:36])[CH:24]=[CH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[C@@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13](O)=[O:14])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.Br.[C:71]([N:88]1[CH2:93][CH2:92][NH:91][CH2:90][CH2:89]1)([O:73][CH2:74][CH:75]1[C:87]2[C:82](=[CH:83][CH:84]=[CH:85][CH:86]=2)[C:81]2[C:76]1=[CH:77][CH:78]=[CH:79][CH:80]=2)=[O:72]>C(#N)C>[CH:86]1[C:87]2[CH:75]([CH2:74][O:73][C:71]([N:88]3[CH2:89][CH2:90][N:91]([C:13](=[O:14])[C@@H:12]([N:11]([CH2:10][C:9]4[CH:37]=[CH:38][C:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])=[CH:7][CH:8]=4)[C:23](=[O:36])[CH:24]=[CH:25][C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:34])([F:35])[F:33])=[CH:28][CH:27]=4)[CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH2:92][CH2:93]3)=[O:72])[C:76]3[C:81](=[CH:80][CH:79]=[CH:78][CH:77]=3)[C:82]=2[CH:83]=[CH:84][CH:85]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 16213207HCID 16213207, compoundHCID 67005271HCID 67005271, compound

Product 1

HCID 67005749HCID 67005749, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-{(4-pentyl-benzyl)-[3-(4-trifluoromethyl-phenyl)-acryloyl]-amino}-(S)-3-phenyl-propionic acid (1.5 g, 2.86 mmol) and TBTU (1.1 g, 3.43 mmol) was dissolved in acetonitrile (30 mL) and DIPEA (1.5 mL, 8.6 mmol) and stirred at rt for 5 min, followed by the addition of Fmoc-piperazine hydrobromide (1.22 g, 3.15 mmol). The reaction mixture was stirred at rt for 16 h and concentrated under reduced pressure. The residue was dissolved in EtOAc (150 ml) and washed with brine (100 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (silicagel, EtOAc/heptane=3/7) to give 1.75 g (75%) of 4-(2-{(4-pentyl-benzyl)-[3-(4-trifluoromethyl-phenyl)-acryloyl]-amino}-(S)-3-phenyl-propionyl)-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester. LC-MS: tR=1.25 min; [M+H]+=814.5.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in EtOAc (150 ml)
  3. washwashed with brine (100 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silicagel, EtOAc/heptane=3/7)

Sources & evidence

ORD record
ord-883f7c227fa247b7a7a3c941d3e123b4
Source dataset
uspto-grants-2011_11
Patent number
US08067419B2

Reaction notes

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