1-Butanol → 4-{5-[Bis-(chloroethyl)-amino]-1-methyl-1H-benzimidazol-2-yl}butyric acid butyl ester

HRID 1746113

Reaktionsgleichung

Reaktionsgleichung von HRID 1746113
[CH3:1][N:2]1[C:10]([CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[N:9][C:8]2[CH:7]=[C:6]([N:17]([CH2:21][CH2:22][Cl:23])[CH2:18][CH2:19][Cl:20])[CH:5]=[CH:4][C:3]1=2.Cl.[CH2:25](O)[CH2:26][CH2:27][CH3:28].C1(N=C=NC2CCCCC2)CCCCC1>CN(C1C=CN=CC=1)C>[CH2:25]([O:15][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][C:10]1[N:2]([CH3:1])[C:3]2[CH:4]=[CH:5][C:6]([N:17]([CH2:18][CH2:19][Cl:20])[CH2:21][CH2:22][Cl:23])=[CH:7][C:8]=2[N:9]=1)[CH2:26][CH2:27][CH3:28]

Komponenten

5

Edukt 3

HCID 2631-ButanolHCID 10868DicyclohexylcarbodiimideHCID 77082Bendamustine Hydrochloride

Produkt 1

HCID 901357594-{5-[Bis-(chloroethyl)-amino]-1-methyl-1H-benzimidazol-2-yl}butyric acid butyl esterAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 142844-(Dimethylamino)pyridineKatalysator

Versuchsvorschrift

A 250 mL three neck round bottom flask was equipped with an overhead stirrer, thermocouple, temperature controller and nitrogen sweep then charged with 10.0 g (25.34 mmol) of bendamustine hydrochloride, 1.9 g (2.35 mL, 25.6 mmol, 1.01 eq) of 1-butanol, 5.3 g (25.6 mmol, 1.01 eq) of dicyclohexylcarbodiimide (DCC), 100 mL of MDC and 0.31 g (2.54 mmol, 0.1 eq) of DMAP. The reaction was stirred at room temperature overnight at which time an in process analysis indicated the reaction was complete. Solids were removed by vacuum filtration and washed with 25 mL of MDC. The filtrate was washed with saturated aqueous sodium bicarbonate solution (2×100 mL), DI water (1×100 mL) and brine (1×100 mL) before drying over sodium sulfate, filtering and concentrating to dryness in vacuo to a brown oil. The oil was triturated with 25 mL of MDC and the solid impurities were removed by vacuum filtration and washed with 25 mL of MDC. The filtrate was concentrated to dryness in vacuo to yield 9.5 g (22.8 mmol, 90%) of the product as a clear light brown oil with an HPLC purity of 94.5A %. 1H NMR (400 MHz, CDCl3) δ 7.17 (d, J=8.76 Hz, 1H), 7.08 (d, J=2.32 Hz, 1H), 6.77 (dd, J=2.36, 8.8 Hz, 1H), 4.05 (t, J=6.76 Hz, 2H), 3.72 (m, 4H), 3.69 (s, 3H), 3.63 (m, 4H), 2.91 (t, J=7.4 Hz, 2H), 2.49 (t, J=7.1 Hz, 2H), 2.18 (m, 2H), 1.60 (m, 2H), 1.32 (m, 2H), 0.89 (t, J=4.56 Hz, 3H).

Aufarbeitung

  1. customSolids were removed by vacuum filtration
  2. washwashed with 25 mL of MDC
  3. washThe filtrate was washed with saturated aqueous sodium bicarbonate solution (2×100 mL), DI water (1×100 mL) and brine (1×100 mL)
  4. dry with materialbefore drying over sodium sulfate
  5. filtrationfiltering
  6. concentrationconcentrating to dryness in vacuo to a brown oil
  7. customThe oil was triturated with 25 mL of MDC
  8. customthe solid impurities were removed by vacuum filtration
  9. washwashed with 25 mL of MDC
  10. concentrationThe filtrate was concentrated to dryness in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-9238756a9a1e4f0896866370f599d7f8
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09149464B2

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