Cesium carbonate → HCID 57637316, compound

HRID 2078747Notes

Reaction equation

HRID 2078747 reaction equation
C(=[N:14][N:15]=[CH:16][C:17]1[S:18][C:19]([CH2:23][O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:20][C:21]=1Br)(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1(P[C-]2C=CC=C2)C=CC=CC=1.[C-]1(PC2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:25]([O:24][CH2:23][C:19]1[S:18][C:17]2[CH:16]=[N:15][NH:14][C:21]=2[CH:20]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 2

HCID 10796Cesium carbonateHCID 76571859HCID 76571859, compound2×

Product 1

HCID 57637316HCID 57637316, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 133083342Bis(cyclopenta-2,4-dien-1-yl(phenyl)phosphane);iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To N-benzhydrylidene-N′-[1-(5-benzyloxymethyl-3-bromo-thiophen-2-yl)-methylidene]-hydrazine (34 g, 69.5 mmol, Intermediate (88)] in toluene (500 mL) were added hydrazone benzophenone (16.4, 83.4 mmol), cesium carbonate (38.4 g, 118.2 mmol), 1,1′ diphenylphosphinoferrocene (5.8 g, 10.4 mmol), and palladium (II) acetate (1.17 g, 5.2 mmol). The suspension was stirred at 90° C. under nitrogen atmosphere until reaction is complete. The solvent was removed. The residual oil was chromatographed (ethyl acetate/n-heptane, 10/90 as eluant) to product an orange oil. It was dissolved in ethanol (350 mL). Concentrated hydrochloric acid (100 mL) was added. The dark mixture was stirred at 80° C. for 15 hours then diluted with water. It was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed through silica gel (n-heptane/ethyl acetate, 80/20 then 50/50 as eluant) to afford 5-benzyloxymethyl-1H-thieno[3,2-c]pyrazole [5.2 g, 37%, Intermediate (89)] as an orange powder. LC/MS: 245.1 (M+H), RT=2.83 minutes. 1H NMR [300 Mhz, (CD3)2SO]: tautomer 1: δ 12.97 (s, 1H), 7.73 (s, 1H), 7.40-7.25 (m, 5H), 7.15-7.05 (m, 1H), 4.71 (s, 2H), 4.55 (s, 2H) tautomer 2: δ 13.27 (brs, 1H), 7.98 (s, 1H), 7.40-7.25 (m, 5H), 7.15-7.05 (m, 1H), 4.71 (s, 2H), 4.55 (s, 2H).

Workup

  1. customThe solvent was removed
  2. customThe residual oil was chromatographed (ethyl acetate/n-heptane, 10/90 as eluant) to product an orange oil
  3. dissolutionIt was dissolved in ethanol (350 mL)
  4. additionConcentrated hydrochloric acid (100 mL) was added
  5. stirringThe dark mixture was stirred at 80° C. for 15 hours
  6. additionthen diluted with water
  7. extractionIt was extracted with ethyl acetate
  8. dry with materialThe organic layer was dried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue was chromatographed through silica gel (n-heptane/ethyl acetate, 80/20

Sources & evidence

ORD record
ord-e2f76b85d55f42619161ebc34df8356d
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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