1,2-Dichloroethane → N-(1-Naphthylmethyl)-N-[2(S)-((imidazol-4-ylacetyl)-amino)-3(S)-methylpentyl]-glycyl-methionine methyl ester

HRID 1900635Notes

Reaction equation

HRID 1900635 reaction equation
[NH:1]1[CH:5]=[C:4]([CH2:6][C:7]([OH:9])=O)[N:3]=[CH:2]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH3:25][O:26][C:27](=[O:56])[C@H:28]([CH2:52][CH2:53][S:54][CH3:55])[NH:29][C:30](=[O:51])[CH2:31][N:32]([CH2:44][C@@H:45]([NH2:50])[CH:46]([CH3:49])[CH2:47][CH3:48])[CH2:33][C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=1.CCN(CC)CC>CN(C=O)C>[CH3:25][O:26][C:27](=[O:56])[C@H:28]([CH2:52][CH2:53][S:54][CH3:55])[NH:29][C:30](=[O:51])[CH2:31][N:32]([CH2:33][C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=1)[CH2:44][C@@H:45]([NH:50][C:7](=[O:9])[CH2:6][C:4]1[N:3]=[CH:2][NH:1][CH:5]=1)[C@@H:46]([CH3:49])[CH2:47][CH3:48]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 96215Imidazole-4-acetic acidHCID 67553617HCID 67553617, compound

Product 1

HCID 178455887N-(1-Naphthylmethyl)-N-[2(S)-((imidazol-4-ylacetyl)-amino)-3(S)-methylpentyl]-glycyl-methionine methyl esterYield 42.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Imidazoleacetic acid (0.064 g, 0.395 mmol), dissolved in DMF (5 mL) was treated with HOBT (0.053 g, 0.40 mmol), EDC (0.076 g, 0.40 mmol), and N-[2(S)-amino-3-methylpentyl)-N-(1-naphtylmethyl)glycyl-methionine methyl ester hydrochloride (0.175 g, 0.329 mmol). The pH was adjusted to 7.5 with Et3N (0.15 mL, 1.1 mmol) and the mixture was stirred at ambient temperature for 24 h. After concentration, and the mixture was partitioned between EtOAc (20 mL) and saturated NaHCO3 solution (10 mL). The aqueous layer was washed with EtOAc (1×20 mL). The organic layers were combined, washed with brine (1×10 m), dried (Na2SO4), filtered and concentrated to give 0.170 g of crude product. Purification by chromatography (silica gel, eluting with 1 to 3% methanol in methylene chloride) gave 0.080 g of pure product. 1H NMR (CD3OD); δ8.30-8.25 (d, 1H, J=9 Hz), 7.91-7.86 (d, 1H, J=6 Hz), 7.85-7.79 (d, 1H, J=9 Hz), 7.56 (s, 1H), 7.55-7.38 (m, 4H), 6.9 (s, 1H), 4.37-4.27 (m, 1H), 4.23-4.04 (m, 3H), 3.67 (s, 3H), 3.49 (ABq, 2H), 3.25 (ABq, 2H), 2.90-2.70 (m, 2H), 2.21-1.97 (m, 2H), 1.95 (s, 3H), 1.88-1.74 (m, 1H), 1.64-1.46 (m, 2H), 1.44-1.25 (m, 1H), 1.14-0.98 (m, 1H), 0.93-0.77 (m, 6H).

Workup

  1. concentrationAfter concentration
  2. customthe mixture was partitioned between EtOAc (20 mL) and saturated NaHCO3 solution (10 mL)
  3. washThe aqueous layer was washed with EtOAc (1×20 mL)
  4. washwashed with brine (1×10 m)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give 0.170 g of crude product
  9. customPurification
  10. washby chromatography (silica gel, eluting with 1 to 3% methanol in methylene chloride)

Sources & evidence

ORD record
ord-6378c8e606004a9884b5568616ca2185
Source dataset
uspto-grants-1996_11
Patent number
US05576293

Reaction notes

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