Diisopropylethylamine → HCID 70058823, compound

HRID 2230309Notes

Reaction equation

HRID 2230309 reaction equation
[N:1]1([C:8]([NH:10][C@@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:38]([O:42][C:43](=[O:61])[C@@H:44]([NH2:60])[CH2:45][C:46]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=2)=[CH:48][CH:47]=1)([CH3:41])([CH3:40])[CH3:39]>C1COCC1>[C:38]([O:42][C:43](=[O:61])[CH:44]([NH:60][C:12](=[O:14])[CH:11]([NH:10][C:8]([N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)=[O:9])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:45][C:46]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=2)=[CH:48][CH:47]=1)([CH3:41])([CH3:39])[CH3:40]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7530182(2S)-2-(azepane-1-carbonylamino)-4-methylpentanoic acidHCID 70059316HCID 70059316, compound

Product 1

HCID 70058823HCID 70058823, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The product from Example Z (1.15 g, 4.50 mmol) was dissolved in 50 mL of THF at room temperature with stirring. To the solution were added O-(7-azabenzotriazol-1-y-)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 3.11 g, 8.18 mmol), 1-hydroxy-7-azabenzotriazole (HOAt, 1.11 g, 8.18 mmol), N,N-diisopropylethylamine (DIEA, 2.84 mL, 16.36 mmol) followed by the product from Example M (1.34 g, 4.09 mmol) in 50 mL of THF. After 3 hours, the solution was concentrated under reduced pressure, partitioned between ethyl ether and water (100 mL each), and separated. The organic layer was washed with 5% sodium bicarbonate (2×50 mL), brine (2×50 mL), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a solid. The solid was purified by silica gel chromatography with ethyl acetate. Appropriate fractions were combined and concentrated under reduced pressure to a solid (2.17 g).

Workup

  1. concentrationthe solution was concentrated under reduced pressure
  2. custompartitioned between ethyl ether and water (100 mL each)
  3. customseparated
  4. washThe organic layer was washed with 5% sodium bicarbonate (2×50 mL), brine (2×50 mL)
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a solid
  8. customThe solid was purified by silica gel chromatography with ethyl acetate
  9. concentrationconcentrated under reduced pressure to a solid (2.17 g)

Sources & evidence

ORD record
ord-c9ba4c3203b84dc8a82a86689f5f0769
Source dataset
uspto-grants-2002_07
Patent number
US06423689B1

Reaction notes

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