Diisopropylethylamine → HCID 54019933, compound

HRID 1953920Notes

Reaction equation

HRID 1953920 reaction equation
[C:1]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]([CH3:19])[C@@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)=[CH:7][CH:6]=1)([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.[NH2:55][CH:56]([CH2:69][C:70]1[CH:75]=[CH:74][C:73]([O:76][CH2:77][C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)=[CH:72][CH:71]=1)[C:57]([NH:59][CH:60]1[CH2:65][CH2:64][CH2:63][N:62]([CH2:66][CH2:67][CH3:68])[CH2:61]1)=[O:58]>CN(C=O)C.C(OCC)(=O)C>[CH2:77]([O:76][C:73]1[CH:74]=[CH:75][C:70]([CH2:69][CH:56]([NH:55][C:12](=[O:14])[CH:11]([N:10]([CH2:9][C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:21][CH:20]=2)[CH3:19])[CH2:15][CH:16]([CH3:18])[CH3:17])[C:57](=[O:58])[NH:59][CH:60]2[CH2:65][CH2:64][CH2:63][N:62]([CH2:66][CH2:67][CH3:68])[CH2:61]2)=[CH:71][CH:72]=1)[C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23297590HCID 23297590, compoundHCID 54066020HCID 54066020, compound

Product 1

HCID 54019933HCID 54019933, compoundYield 23.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-[(4-tert-butyl-benzyl)-methyl-amino]-4-methyl-pentanoic acid (0.3 g, 1.01 mmol) in 15 mL of DMF was added HBTU (0.38 g, 1.01 mmol) and diisopropylethylamine (0.65 g, 5.05 mmol). The mixture was stirred for 30 minutes at 0° C. A solution of 2-amino-3-(4-benzyloxyphenyl)-N-(1-propyl-piperidin-3-yl)propionamide (0.4 g, 1.01 mmol) in 15 mL of DMF was added to the reaction mixture. The reaction mixture was allowed to warm to room temperature and was stirred for another 30 minutes. The mixture was diluted with 20 mL of ethyl acetate, washed with 1N HCl (2×10 mL), saturated NaHCO3 (2×10 mL) and saturated solution of brine (2×10 mL). The organic layer was separated, dried with Na2SO4 and evaporated to dryness. The crude residue was purified by chromatography (silica gel, 7:3 hexane/ethyl acetate). The purified product was dissolved in minimum volume of diethylether and an ethereal solution of HCl was added dropwise. The solid which formed was washed several times with diethylether. The solid was dissolved in methanol and treated with activated charcoal, filtered, and evaporated. The residue was crystallized from methanol-ether to give the title compound (0.16 g, 23%) as a light yellow powder; mp 160-164° C. (dec).

Workup

  1. temperatureto warm to room temperature
  2. stirringwas stirred for another 30 minutes
  3. washwashed with 1N HCl (2×10 mL), saturated NaHCO3 (2×10 mL) and saturated solution of brine (2×10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried with Na2SO4
  6. customevaporated to dryness
  7. customThe crude residue was purified by chromatography (silica gel, 7:3 hexane/ethyl acetate)
  8. dissolutionThe purified product was dissolved in minimum volume of diethylether
  9. additionan ethereal solution of HCl was added dropwise
  10. customThe solid which formed
  11. washwas washed several times with diethylether
  12. dissolutionThe solid was dissolved in methanol
  13. additiontreated with activated charcoal
  14. filtrationfiltered
  15. customevaporated
  16. customThe residue was crystallized from methanol-ether

Sources & evidence

ORD record
ord-c80beb4a5c9544d0ac0831c76c83b74b
Source dataset
uspto-grants-2000_09
Patent number
US06117841

Reaction notes

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