Water → methyl 1-[(2-fluoro-3-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate

HRID 539184

Reaktionsgleichung

Reaktionsgleichung von HRID 539184
[CH3:1][C:2]1[NH:6][C:5]2[C:7]([C:17]([O:19][CH3:20])=[O:18])=[CH:8][C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:10][C:4]=2[N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:30]=1[F:36].O>CN(C=O)C>[F:36][C:30]1[C:31]([CH3:35])=[CH:32][CH:33]=[CH:34][C:29]=1[CH2:28][N:3]1[C:4]2[CH:10]=[C:9]([N:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)[CH:8]=[C:7]([C:17]([O:19][CH3:20])=[O:18])[C:5]=2[N:6]=[C:2]1[CH3:1]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 519062Benzene, 1-(bromomethyl)-2-fluoro-3-methyl-HCID 178498372HCID 178498372, Verbindung

Produkt 1

HCID 56959682methyl 1-[(2-fluoro-3-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylateAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate prepared as described in Example 26, step d (500 mg, 1.82 mmol), K2CO3 (502 mg, 3.64 mmol) and 1-(bromomethyl)-2-fluoro-3-methylbenzene (389 mg, 1.91 mmol) in DMF (25 mL) was stirred at 80° C. for 18 h. The reaction mixture was cooled, poured into water (100 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel chromatography eluted with EtOAc:MeOH=100:1 to give the desired product (350 mg, 48%) as a red solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.24 (d, 3H, J=1.8 Hz), 2.47 (s, 3H), 3.09 (t, 4H, J=4.8 Hz), 3.75 (t, 4H, J=4.8 Hz), 3.86 (s, 3H), 5.51 (s, 2H), 6.62 (t, 1H, J=7.5 Hz), 7.00 (t, 1H, J=7.5 Hz), 7.22 (t, 1H, J=7.5 Hz), 7.32 (d, 1H, J=2.4 Hz), 7.36 (d, 1H, J=2.4 Hz); LC-MS: m/e=398 [M+1]+

Aufarbeitung

  1. customprepared
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted with EtOAc (50 mL×3)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel chromatography
  7. washeluted with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-fe7a9e71468f4c09b7b9b79732985b7d
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865912B2

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