Cesium carbonate → HCID 10128697, compound

HRID 916947Notes

Reaction equation

HRID 916947 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:14][C:13](=[O:15])[C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=1[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1.[F:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][C:35]=1[F:36])[CH2:31]Br.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[F:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][C:35]=1[F:36])[CH2:31][O:15][C:13]1[C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]([C:20]2[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=2)=[C:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[N:14]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 69416016HCID 69416016, compound

Product 1

HCID 10128697HCID 10128697, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 6-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate (300 mg, 0.73 mmol) from Example 51, Step A in DMF (3 mL) was added 3,4-difluorobenzyl bromide (0.122 mL, 0.95 mmol) and then cesium carbonate (310 mg, 0.95 mmol). The reaction was stirred at 50° C. for 3 h and was then diluted with water and extracted three times with methylene chloride. The organic layers were washed with a portion of brine and the combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to give the crude products. The products were separated by preparative TLC (3×1 mm) eluted with 25% ethyl acetate in hexanes to yield faster eluting O-alkylation title product. HPLC/MS: 534 (M+1), 536 (M+3); Rt=5.17 min. 1HNMR (CDCl3): δ 3.981 (s, 3H), 5.489 (s, 2H), 7.04 (br d, J=8.4 Hz, 2H), 7.11 (d, J=8.2 Hz, 1H), 7.2-7.6 (m, 3H), 7.38 (d, J=2.0 Hz, 1H), 8.285 (s, 1H).

Workup

  1. extractionextracted three times with methylene chloride
  2. washThe organic layers were washed with a portion of brine
  3. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bcda0a0a83124506ac1c3591f3b50df0
Source dataset
uspto-grants-2007_09
Patent number
US07271266B2

Reaction notes

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