Cesium carbonate → Ethyl 3-(5-cyano-1H-indazol-1-yl)propanoate

HRID 2189777Notes

Reaction equation

HRID 2189777 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]#[N:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].ClCCC(OCC)=O>CN(C=O)C>[C:10]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[N:1]([CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:2]=[CH:3]2)#[N:11]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 68320Ethyl 3-bromopropionateHCID 69341Ethyl 3-chloropropionateHCID 111263841H-Indazole-5-carbonitrile

Product 1

HCID 59316705Ethyl 3-(5-cyano-1H-indazol-1-yl)propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1H-indazole-5-carbonitrile (D1) (3.88 g, 27.3 mmol) in DMF (85 ml) was added Cs2CO3 (17.8 g, 54.6 mmol) and then ethyl 3-bromopropanoate (3.5 ml), 27 mmol) and ethyl 3-chloropropanoate (3.3 g, 24.2 mmol) were added. The reaction mixture was stirred at 80° C. for 4 hours and then allowed to cool. The solvent was removed in vacuo and the crude material was partitioned between EtOAc and water, the organics were separated, washed with brine, dried and evaporated. The crude was azeotroped with toluene and then purified by flash chromatography (EtOAc/hexane 1:9 to 1:1) to give 3.84 g of a yellow gum. MS data as for previous example.

Workup

  1. temperatureto cool
  2. customThe solvent was removed in vacuo
  3. customthe crude material was partitioned between EtOAc and water
  4. customthe organics were separated
  5. washwashed with brine
  6. customdried
  7. customevaporated
  8. customThe crude was azeotroped with toluene
  9. custompurified by flash chromatography (EtOAc/hexane 1:9 to 1:1)

Sources & evidence

ORD record
ord-97f1972c2270450ca4de36af76a67eca
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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