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

HRID 1599699Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1599699
[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

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

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

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7a57015e50f54811ac93c893b092d66c
Quelldatensatz
uspto-grants-1998_04
Patentnummer
US05741792

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