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

HRID 2189778Notes

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]>CN(C)C=O.CCOC(C)=O>[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

Conditions

Temperature: 80 °C

Procedure

1H-indazole-5-carbonitrile (D1) (3.5 g, 24.45 mmol) was dissolved in N,N-dimethylformamide (60 ml). cesium carbonate (15.93 g, 48.9 mmol) and ethyl 3-bromopropanoate (4.68 ml, 36.7 mmol) were added. The mixture was heated at 80° C. for 4 hours. Diluted with EtOAc and washed with water (3×40 ml), dried over MgSO4 and evaporated. The mixture was purified by flash chromatography, eluting EtOAc/iso-Hexane 10-30% then 10-20% to give (3.682 g) for the first isomer (yellow oil) and (1.509 g) for the second isomer (pink solid). Analysis of the first isomer by 1H nmr indicated that is was the 1-isomer contaminated with the 2-isomer (ca. 20%) δH (d6-DMSO, 400 MHz) 1.05 (3H, t), 2.95 (2H, t), 3.97 (2H, q), 4.69 (2H, t), 7.74 (1H, dd), 7.92 (1H, dt), 8.28 (1H, d), 8.38 (1H, dd). MS (ES+): C13H13N3O2 requires 243; found (MH+) 244.

Workup

washwashed with water (3×40 ml)
dry with materialdried over MgSO4
customevaporated
customThe mixture was purified by flash chromatography
washeluting EtOAc/iso-Hexane 10-30%
custom10-20% to give (3.682 g) for the first isomer (yellow oil) and (1.509 g) for the second isomer (pink solid)

Sources & evidence

ORD record: ord-500a158a08024a3bb41f610e48df533d
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324254B2

Reaction notes

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