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

HRID 1900635ノート

反応式

HRID 1900635 の反応式
[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]

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6378c8e606004a9884b5568616ca2185
出典データセット
uspto-grants-1996_11
特許番号
US05576293

反応ノート

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