Toluene → [3-(N'-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-1H-benzoimidazol-2-yl)-methanone

HRID 2111158Notes

Reaction equation

HRID 2111158 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[C:19]([C:21]1[S:22][CH:23]=[CH:24][C:25]=1Br)=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27](=[N:40][NH2:41])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:27](=[N:40][NH:41][C:25]1[CH:24]=[CH:23][S:22][C:21]=1[C:19]([C:11]1[N:10]([CH2:9][O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=1)=[O:20])([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 79304DiphenylmethylidenehydrazineHCID 57637380(1-benzyloxymethyl-1H-benzimidazol-2-yl)-(3-bromothiophen-2-yl)methanone

Product 1

HCID 57637293[3-(N'-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-1H-benzoimidazol-2-yl)-methanone

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (1-benzyloxymethyl-1H-benzimidazol-2-yl)-(3-bromothiophen-2-yl)methanone (500 mg, 1.06 mmol, Example 1C), benzophenone hydrazone (276 mg, 1.41 mmol), palladium(II) acetate (13.4 mg, 0.06 mmol), 1,1′-Bis(diphenylphosphino)-ferrocene (57.5 mg, 0.104 mmol), cesium carbonate (570 mg, 1.75 mmol), and toluene (10 mL) under nitrogen is stirred at 90° C. for 15 hours. The dark reaction is cooled to ambient temperature, diluted with ethyl acetate, filtered, and the insolubles washed with ethyl acetate. The combined filtrate and washings were washed with water and brine successively, dried over magnesium sulfate, and then concentrated under reduced pressure to afford a yellow oil. The crude material is chromatographed on silica, eluting with 80% dichloromethane/heptane, to give [3-(N′-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-1H-benzoimidazol-2-yl)-methanone as a yellow-orange powder: TLC Rƒ0.30 (silica, 80% dichloromethane/heptane); LC/MS: (M+H 543.1, RT=4.68 minutes); 1H NMR [(CD3)2SO), 300 MHz]: δ 11.64 (s, 1H), 8.08 (d, 1H, 5.5 Hz), 7.84-7.13 (m, 20 H), 6.00 (s, 2H), 4.46 (s, 2H).

Workup

  1. customThe dark reaction
  2. temperatureis cooled to ambient temperature
  3. filtrationfiltered
  4. washthe insolubles washed with ethyl acetate
  5. washThe combined filtrate and washings were washed with water and brine successively
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto afford a yellow oil
  9. customThe crude material is chromatographed on silica
  10. washeluting with 80% dichloromethane/heptane

Sources & evidence

ORD record
ord-4bf1811a2f4e446d91f7ab125038f722
Source dataset
uspto-grants-2009_04
Patent number
US07518000B2

Reaction notes

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