Triethylamine → ethyl 3-(1-acetyl-1H-indazol-5-yl)-3-oxopropanoate
Reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([OH:15])=O)=[CH:10][CH:11]=2)[CH:6]=[N:5]1)(=[O:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:28]([O:30][C:31](=[O:36])[CH2:32]C(O)=O)[CH3:29].CCN(CC)CC.[Mg+2].[Cl-].[Cl-].[K]>O1CCCC1.C(#N)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH2:32][C:31]([O:30][CH2:28][CH3:29])=[O:36])=[CH:10][CH:11]=2)[CH:6]=[N:5]1)(=[O:3])[CH3:2]Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 40 °C
Procedure
To a solution of 1-acetyl-1H-indazole-5-carboxylic acid (8.5 g, 41.63 mmol) in tetrahydrofuran (200 ml) was added CDI (20 g), and the resulting mixture was stirred for 2.5 h at 40° C., and then added dropwise to a solution of the magnesium salt of malonic acid monoethyl ester [prepared via the addition of Et3N (14 g, 138.25 mmol) and MgCl2 (19 g, 200 mmol) to a solution of potassium monoethylonate (24 g, 147.17 mmol) in acetonitrile (200 ml)] followed by stirring at room temperature for 2.5 h at 0° C. The resulting solution was stirred for an additional 2.5 h at 80° C. The reaction was then quenched by the addition of water (500 ml) and the pH adjusted to 3 with HCl (3N). The solids were collected by filtration and washed with water (3×50 ml) to afford ethyl 3-(1-acetyl-1H-indazol-5-yl)-3-oxopropanoate as a light yellow solid (8.6 g, 75%).
Workup
- stirringby stirring at room temperature for 2.5 h at 0° C
- stirringThe resulting solution was stirred for an additional 2.5 h at 80° C
- customThe reaction was then quenched by the addition of water (500 ml)
- filtrationThe solids were collected by filtration
- washwashed with water (3×50 ml)
Sources & evidence
- ORD record
- ord-cc4d2f352bd943babfab5c2b03b8e158
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09278973B2
Reaction notes
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