Water → 1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carbonitrile

HRID 2088555Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2088555
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=3[Cl:20])[C:6]=2[CH:5]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:3]=1.O.[CH3:28][N:29](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2].[Zn]>[Cl:20][C:14]1[C:15]([Cl:19])=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:7]1[C:6]2[CH:5]=[C:4]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH:3]=[C:2]([C:28]#[N:29])[C:10]=2[N:9]=[C:8]1[CH3:11]

Komponenten

8

Edukt 3

HCID 962WaterHCID 6228DimethylformamideHCID 669767924-(4-bromo-1-(2,3-dichlorobenzyl)-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine

Produkt 1

HCID 569596841-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carbonitrileAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 23994ZincKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-bromo-1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole (1 g, 2.2 mmol), Pd(dba)2 (161 mg, 0.22 mmol), dppf (244 mg, 0.44 mmol), Zn(CN)2 (1030 mg, 8.8 mmol), water (1 mL), Fe(OAc)2 (191 mg, 1.1 mmol) and Zn powder (429 mg, 6.6 mmol) in DMF (50 mL) was stirred at 100° C. under N2 for 20 h. When TLC showed no starting material remaining, the reaction mixture was quenched with water and extracted with EtOAc (100 mL×3). The organic layer was washed with brine, dried over MgSO4, concentrated. The resulting residue was purified by silica gel chromatography eluted with EtOAc to give the product (400 mg, 45%), as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.11 (t, 4H, J=4.8 Hz), 3.72 (t, 4H, J=4.8 Hz), 5.60 (s, 2H), 6.30 (dd, 1H, J=1.2, 8.1 Hz), 7.25 (t, 1H, J=8.1 Hz), 7.35 (d, 1H, J=2.1 Hz), 7.42 (d, 1H, J=2.1 Hz), 7.60 (dd, 1H, J=1.2, 8.1 Hz); LC-MS: m/e=401 [M+1]+.

Aufarbeitung

  1. customthe reaction mixture was quenched with water
  2. extractionextracted with EtOAc (100 mL×3)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel chromatography
  7. washeluted with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-4b46f4ff041a445197d7b6fcaab62281
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08435988B2

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