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

HRID 1900635노트

반응식

HRID 1900635 반응식
[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]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 962151H-Imidazole-5-acetic acidHCID 67553617HCID 67553617, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6378c8e606004a9884b5568616ca2185
출처 데이터셋
uspto-grants-1996_11
특허 번호
US05576293

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