4-Methylmorpholine → N-[[1-(Aminoiminomethyl)-4-piperidinyl]methyl]-1-[N-(methylsulfonyl)-D-phenylalanyl]-L-prolinamide

HRID 1599699ノート

反応式

HRID 1599699 の反応式
[CH3:1][S:2]([NH:5][C@@H:6]([C:14]([N:16]1[CH2:23][CH2:22][CH2:21][C@H:17]1[C:18]([OH:20])=O)=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:4])=[O:3].[NH2:24][CH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32](=[NH:34])N)[CH2:28][CH2:27]1.C1C=CC2N(O)N=[N:41]C=2C=1.CN1CCOCC1>C(O)(C)C.O>[NH2:41][N:34]=[CH:32][N:29]1[CH2:30][CH2:31][CH:26]([CH2:25][NH:24][C:18](=[O:20])[C@@H:17]2[CH2:21][CH2:22][CH2:23][N:16]2[C:14](=[O:15])[C@@H:6]([CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:27][CH2:28]1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27565044-(Aminomethyl)piperidine-1-carboximidamideHCID 10893176N-methylsulfonyl-D-phenylalanyl-proline

生成物 1

HCID 70061377N-[[1-(Aminoiminomethyl)-4-piperidinyl]methyl]-1-[N-(methylsulfonyl)-D-phenylalanyl]-L-prolinamide収率 90%

試薬・触媒・溶媒 1

HCID 21889133Propan-2-ol--water (1/1)溶媒

反応条件

温度
0 °C

実験手順

To a suspension of N-methylsulfonyl-D-phenylalanyl-proline (497 mg, 1.46 mmol), 4-(aminomethyl)-1-piperidinecarboximidamide (470 mg, 1.9 mmol) and HOBt (217 mg, 1.6 mmol) in 1:1 v/v isopropyl alcohol/water (4.5 mL) was added NMM (0.32 mL, 2.9 mmol). The homogeneous solution was cooled to 0° C. and ethyl-3-(3-dimethylamino)-propylcarbodiimide·hydrochloride salt (EDAC·HCl) (308 mg, 1.6 mmol) was added. After 18 hr the reaction was concentrated in vacuo, dissolved in water (10 mL) and washed with ether (2×75 mL). Aqueous NaOH (1 N, 3.8 mL) was added until the aqueous layer attained pH 9.7, the aqueous layer was washed with ether (75 mL) and the process repeated. Aqueous HCl (1N, 3.8 mL) was added until the pH reached 2.0, the aqueous layer was washed with ethyl acetate (3×75 mL), concentrated in vacuo, dissolved in water, and lyophilized to give a foam which was subjected to chromatography on HP-20 polystyrene resin to provide the title compound (629 mg, 84%).

後処理

  1. concentrationAfter 18 hr the reaction was concentrated in vacuo
  2. dissolutiondissolved in water (10 mL)
  3. washwashed with ether (2×75 mL)
  4. additionAqueous NaOH (1 N, 3.8 mL) was added until the aqueous layer
  5. washthe aqueous layer was washed with ether (75 mL)
  6. additionAqueous HCl (1N, 3.8 mL) was added until the pH
  7. washthe aqueous layer was washed with ethyl acetate (3×75 mL)
  8. concentrationconcentrated in vacuo
  9. dissolutiondissolved in water
  10. customto give a foam which

出典と根拠

ORDレコード
ord-7a57015e50f54811ac93c893b092d66c
出典データセット
uspto-grants-1998_04
特許番号
US05741792

反応ノート

読み込み中…