Dimethylformamide → {1-[2-[2-Ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl carbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester

HRID 720187Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 720187
Cl.[NH2:2][CH:3]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]([CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[C:13]([NH:15][CH3:16])=[O:14])[CH2:8][CH:7]1[CH2:28][CH3:29])=[O:5].[C:38]([O:42][C:43](CC(N)(C)C(O)=O)=[O:44])([CH3:41])([CH3:40])[CH3:39].O[N:53]1[C:57]2[CH:58]=CC=C[C:56]=2N=N1.CN1CCOCC1.CN([CH:72]=[O:73])C>O.CCOC(C)=O>[C:38]([O:42][C:43](=[O:44])[NH:53][C:57]([C:72](=[O:73])[NH:2][CH:3]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]([C:13](=[O:14])[NH:15][CH3:16])[CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[CH2:8][CH:7]1[CH2:28][CH3:29])=[O:5])([CH3:58])[CH3:56])([CH3:39])([CH3:40])[CH3:41]

Komponenten

8

Edukt 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 19692748Boc-aminoisobutyric acidHCID 219015482-{4-[2-amino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propioamide Hydrochloride

Produkt 1

HCID 69587967{1-[2-[2-Ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl carbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2-{4-[2-Amino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propioamide hydrochloride, 41, (0.3 g, 0.6 mmol) and tert-butyloxycarbonyl-α-aminoisobutyric acid (AIB) (0.12 g, 0.6 mmol) 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (0.22 g, 1.1 mmol) and 1-hydroxybenzotriazole (0.1 g, 0.7 mmol) are dissolved in anhydrous DMF (2.5 mL). The reaction mixture is cooled to 0° C., then N-methylmorpholine (0.2 mL, 1.7 mmol) is added. The reaction mixture is placed in refrigerator overnight. EtOAc (25 mL) and water (75 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×30 mL). All organic layers are combined and washed with water (2×50 mL), and dried over Na2SO4. Solvent is removed in vacuo and the product is purified over silica (EtOAc/Hexane, 2/1) to afford 0.7 g of the desired compound. 1H NMR (CDCl3, δ): 7.80–7.58 (m, 4H), 7.42–7.22 (m, 3H), 7.20–7.00 (m, 2H), 6.98–6.50 (m, 2H), 5.40–4.98 (m, 1.5H), 4.70–3.90 (m, 1H), 3.75–3.02 (m, 3.5H), 3.00–2.56 (m, 7H), 2.42–2.35 (m, 1H), 2.18–1.95 (m, 2.5H), 1.50–1.12 (m, 18H), 0.095–0.75 (m, 3H); 13C NMR, δ 174.4, 172.1, 171.9, 170.3, 169.6, 163.7, 162.0, 154.6, 137.3, 133.7, 132.3, 131.4, 130.8, 128.1, 127.8, 127.6, 126.2, 125.6, 115.7, 115.4, 115.2, 80.0, 70.2, 56.7, 55.3, 50.9, 50.0, 49.9, 41.8, 39.5, 38.5, 37.9, 32.7, 32.4, 28.5, 28.3, 26.1, 25.5, 25.3, 23.1, 22.1, 10.6, 10.1.

Aufarbeitung

  1. customis placed in refrigerator overnight
  2. customthe organic layer is separated
  3. extractionThe aqueous layer is extracted with EtOAc (3×30 mL)
  4. washwashed with water (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. customSolvent is removed in vacuo
  7. customthe product is purified over silica (EtOAc/Hexane, 2/1)

Quellen und Nachweise

ORD-Eintrag
ord-2e2e6a967bba42189526f6b6596aa56e
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07132539B2

Notizen zur Reaktion

Wird geladen…