Diisopropylethylamine → 4-[2-(2-{[2-(Tert-butoxycarbonyl-methyl-amino)-acetyl]-methyl-amino}-acetoxy)-4-methyl-pentanoyl]-piperazine-1-carboxylic acid benzyl ester

HRID 2079337Notes

Reaction equation

HRID 2079337 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:18])[CH2:9][C:10]([N:12]([CH2:14][C:15]([OH:17])=[O:16])[CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH2:52]([O:59][C:60]([N:62]1[CH2:67][CH2:66][N:65]([C:68](=[O:75])[CH:69](O)[CH2:70][CH:71]([CH3:73])[CH3:72])[CH2:64][CH2:63]1)=[O:61])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>C1COCC1.C(Cl)Cl.O>[CH2:52]([O:59][C:60]([N:62]1[CH2:63][CH2:64][N:65]([C:68](=[O:75])[CH:69]([O:16][C:15](=[O:17])[CH2:14][N:12]([C:10](=[O:11])[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH3:18])[CH3:13])[CH2:70][CH:71]([CH3:72])[CH3:73])[CH2:66][CH2:67]1)=[O:61])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 513582342-(2-((tert-Butoxycarbonyl)(methyl)amino)-N-methylacetamido)acetic acidHCID 670985604-(2-Hydroxy-4-methyl-pentanoyl)-piperazine-1-carboxylic acid benzyl ester

Product 1

HCID 670984054-[2-(2-{[2-(Tert-butoxycarbonyl-methyl-amino)-acetyl]-methyl-amino}-acetoxy)-4-methyl-pentanoyl]-piperazine-1-carboxylic acid benzyl esterYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

To {[2-(tert-butoxycarbonyl-methyl-amino)-acetyl]-methyl-amino}-acetic acid (427 mg, 1.57 mmol) in 2 mL of THF was added sequentially HBTU (624 mg, 1.2 mmol), diisopropyl ethylamine (860 μL, 4.71 mmol) at room temperature. After 5 min, 4-(2-hydroxy-4-methyl-pentanoyl)-piperazine-1-carboxylic acid benzyl ester (403 mg 1.2 mmol) in 2 mL of THF was added to the reaction mixture, and the solution was heated at 65° C. for 12 h. The reaction mixture was cooled and diluted with 20 mL of CH2Cl2 and 10 mL of water. The organic layer was separated and dried over Na2SO4, and the solvent was removed under reduced pressure to give an oil. The residue was subjected to purification by normal phase LC using 30-100% EtOAc-hexanes to give 4-[2-(2-{[2-(tert-butoxycarbonyl-methyl-amino)-acetyl]-methyl-amino}-acetoxy)-4-methyl-pentanoyl]-piperazine-1-carboxylic acid benzyl ester (283 mg, 41% yield). LC/MS: m/z 577 (M+H)+ at 3.43 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed under reduced pressure
  5. customto give an oil
  6. customThe residue was subjected to purification by normal phase LC

Sources & evidence

ORD record
ord-ee43f03b87574e6b8fa50d474ba377b2
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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