Hydrazine hydrate (1:1) → HCID 178506258, Verbindung

HRID 1749624Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1749624
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:17]=[C:18]([C:19]([NH2:21])=O)[C:13]=2[N:12]=[C:11]1[C:28]([F:31])([F:30])[F:29].COC(OC)[N:35]([CH3:37])C.O.[NH2:41]N>>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[CH:17]=[C:18]([C:19]3[N:21]=[CH:37][NH:35][N:41]=3)[C:13]=2[N:12]=[C:11]1[C:28]([F:29])([F:30])[F:31]

Komponenten

4

Edukt 3

HCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 669767431-[(2,3-dichlorophenyl)methyl]-6-(4-morpholinyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxamide

Produkt 1

HCID 178506258HCID 178506258, VerbindungAusbeute 27,6 %

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

A suspension of 1-[(2,3-dichlorophenyl)methyl]-6-(4-morpholinyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxamide, prepared as described in Example 56, step a (389 mg, 0.822 mmol) in N,N-dimethylformamide dimethyl acetal (9 mL, 67.2 mmol) was stirred at 105° C. for 1 hour. The reaction was concentrated under reduced pressure and the residue was suspended in Acetic Acid (7 mL). After the addition of hydrazine monohydrate (0.181 mL, 5.75 mmol) the reaction mixture was heated at 100° C. for 1 hour. The solvent was concentrated under vacuum and the residue was dissolved in DMSO and purified by reverse phase-HPLC (20-95% AcCN in water plus 0.1% TFA) (some residual solid filtered off). The fractions containing product were combined, neutralized by the addition of aq NaHCO3 sat sol and the organic evaporated (some compound lost during transfer). The precipitate in the aqueous residue was collected by filtration, washed with water and dried in a vacuum oven (45° C.) overnight to give the desired product (115 mg, 0.227 mmol, 27.6% yield) as a white powder. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 13.05 (br. s., 1H), 8.12 (s, 1H), 8.00 (d, J=2.27 Hz, 1H), 7.47 (dd, J=8.08, 1.26 Hz, 1H), 7.10 (t, J=7.96 Hz, 1H), 6.59 (d, J=2.27 Hz, 1H), 6.37 (dd, J=7.83, 1.01 Hz, 1H), 5.62 (s, 2H), 3.79-3.92 (m, 4H), 3.17-3.30 (m, 4H). MS(ES+) m/e 497 [M+H]+.

Aufarbeitung

  1. customprepared
  2. concentrationThe reaction was concentrated under reduced pressure
  3. temperaturewas heated at 100° C. for 1 hour
  4. concentrationThe solvent was concentrated under vacuum
  5. dissolutionthe residue was dissolved in DMSO
  6. custompurified by reverse phase-HPLC (20-95% AcCN in water plus 0.1% TFA) (some residual solid
  7. filtrationfiltered off)
  8. additionThe fractions containing product
  9. additionneutralized by the addition of aq NaHCO3
  10. customthe organic evaporated (some compound
  11. filtrationThe precipitate in the aqueous residue was collected by filtration
  12. washwashed with water
  13. customdried in a vacuum oven (45° C.) overnight

Quellen und Nachweise

ORD-Eintrag
ord-0a07c8e8bba043c0854d1a5abc804967
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156797B2

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