Triethylamine → HCID 86632569, compound

HRID 1095393Notes

Reaction equation

HRID 1095393 reaction equation
[N:1]1([CH2:7][CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([C:18]([NH:20][C@H:21]([C:26]([OH:28])=[O:27])[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:19])[C:10]2=[O:29])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.N[C@H](C(OC)=O)C(C)(C)C.O[NH:42][C:43](=[NH:45])[CH3:44].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[NH2:45][C:43](=[N:42][O:27][C:26]([C@@H:21]([NH:20][C:18]([N:11]1[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:9]([CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[C:10]1=[O:29])=[O:19])[C:22]([CH3:23])([CH3:24])[CH3:25])=[O:28])[CH3:44]

Participants

8

Reactant 6

HCID 8471Triethylamine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 757711-Hydroxybenzotriazole2×HCID 16217630Methyl L-tert-leucinate hydrochlorideHCID 66784001HCID 66784001, compoundHCID 178465666HCID 178465666, compound2×

Product 1

HCID 86632569HCID 86632569, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of N-({3-[2-(4-morpholinyl)ethyl]-oxo-2,3-dihydro-1H-benzimidazol-1-yl}carbonyl)-L-tert-leucine (prepared according to the procedure described in step 1 of example 3 from methyl L-tert-leucinate hydrochloride) (0.18 g, 0.45 mmol) in DMF (1 mL) were added a solution of N-hydroxyethanimidamide (37 mg, 0.50 mmol, Hamze, A.; Hernandez, J.-F.; Fulcrand, P.; Martinez, J. J. Org. Chem. 2003, 68, 7316-7321.) in DMF (1 mL), triethylamine (0.26 mL, 1.8 mmol), HOBt (83 mg, 0.54 mmol) and WSC (0.10 g, 0.54 mmol) at rt. After 9 h, to this mixture were added N-hydroxyethanimidamide (20 mg, 0.26 mmol), triethylamine (0.10 mL, 0.70 mmol), HOBt (10 mg, 0.06 mmol) and WSC (20 mg, 0.10 mmol). After 13 h, the reaction was quenched by addition of sat. aq. sodium bicarbonate (10 mL) and extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with water (10 mL×2), brine (20 mL) and dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (10/1) to afford 0.12 g (57%) of the title compound.

Workup

  1. customat rt
  2. waitAfter 13 h
  3. customthe reaction was quenched by addition of sat. aq. sodium bicarbonate (10 mL)
  4. extractionextracted with ethyl acetate (20 mL×2)
  5. washThe combined organic layers were washed with water (10 mL×2), brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (10/1)

Sources & evidence

ORD record
ord-663943a24ac04b208219ed4e9f78717d
Source dataset
uspto-grants-2012_03
Patent number
US08138177B2

Reaction notes

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