Triethylamine → HCID 11553970, compound

HRID 1095378Notes

Reaction equation

HRID 1095378 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[NH:11][C:10]2=[O:18])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[Cl:26][C:27](OC1C=CC([N+]([O-])=O)=CC=1)=[O:28].Cl.[NH2:40][C@H:41]([C:46]([NH2:48])=[O:47])[C@H:42]([CH2:44][CH3:45])[CH3:43]>ClCCl>[ClH:26].[NH2:48][C:46]([C@@H:41]([NH:40][C:27]([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:18])=[O:28])[C@@H:42]([CH3:43])[CH2:44][CH3:45])=[O:47]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 807407HCID 807407, compoundHCID 16219521L-Isoleucinamide--hydrogen chloride (1/1)

Product 1

HCID 11553970HCID 11553970, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(2-morpholin-4-ylethyl)-1,3-dihydro-2H-benzimidazol-2-one (530 mg, 2.1 mmol) in dichloromethane (8 mL) were added triethylamine (1.0 mL, 7.0 mmol) and 4-nitrophenyl chloroformate (470 mg, 2.3 mmol) at 0° C. and the mixture was stirred for 3 h at rt. Then to this mixture was added a mixture of L-isoleucinamide hydrochloride (430 mg, 2.6 mmol) and triethylamine (0.6 mL, 4.3 mmol) in dichloromethane (4 mL) at 0° C. and stirred rt. After 22 h, the reaction was quenched by addition of water (50 mL) and extracted with dichloromethane (50 mL×2). The combined organic layers were washed with water (20 mL×3), brine (20 mL) and dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (1/4) to afford 600 mg (70%) of free form of the title compound. The obtained compound was dissolved in ethyl acetate (1 mL) and to this solution was added 4N HCl in ethyl acetate (0.4 mL) to form white solid which was filtered and dried in vacuo to give the title compound (600 mg).

Workup

  1. additionThen to this mixture was added
  2. stirringstirred rt
  3. waitAfter 22 h
  4. customthe reaction was quenched by addition of water (50 mL)
  5. extractionextracted with dichloromethane (50 mL×2)
  6. washThe combined organic layers were washed with water (20 mL×3), brine (20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (1/4)

Sources & evidence

ORD record
ord-ba174b8b26be4e718b7530c1e8a4d95e
Source dataset
uspto-grants-2012_03
Patent number
US08138177B2

Reaction notes

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