Water → 2-amino-5-[1-(2-oxo-2-piperidin-1-ylethyl)-1H-pyrazol-4-yl]pyridine-3-carbaldehyde

HRID 241406Notes

Reaction equation

HRID 241406 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5](I)=[CH:4][N:3]=1.[N:11]1([C:17](=[O:33])[CH2:18][N:19]2[CH:23]=[C:22](B3OC(C)(C)C(C)(C)O3)[CH:21]=[N:20]2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.C(=O)([O-])[O-].[Na+].[Na+].O>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5]([C:22]2[CH:21]=[N:20][N:19]([CH2:18][C:17](=[O:33])[N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[CH:23]=2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 177501772-Amino-5-iodopyridine-3-carbaldehydeHCID 534020131-(piperidin-1-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethanone

Product 1

HCID 866648052-amino-5-[1-(2-oxo-2-piperidin-1-ylethyl)-1H-pyrazol-4-yl]pyridine-3-carbaldehyde

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

5.1 200 mg (0.806 mmol) of 2-amino-5-iodopyridine-3-carbaldehyde and 501 mg (1.570 mmol) of 1-piperidin-1-yl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]ethanone are dissolved in 4 ml of N,N-dimethylformamide in an argon-filled microwave vessel, and 2.5 ml (5 mmol) of 2M sodium carbonate solution and 93.2 mg (0.081 mmol) of tetrakis(triphenylphosphine)palladium(0) are added. The reaction solution is irradiated with microwaves for 30 min at 120° C. in the Biotage SmithSynthesizer. The reaction mixture is cooled to room temperature, water is added, and the mixture is filtered. The filtrate is extracted three times with ethyl acetate, and the combined organic phases are washed 2× with water, dried using sodium sulfate, and evaporated to dryness. The oily residue is purified by means of RP-HPLC, giving 2-amino-5-[1-(2-oxo-2-piperidin-1-ylethyl)-1H-pyrazol-4-yl]pyridine-3-carbaldehyde as yellowish powder; ESI-MS [M+H]+ 314.2.

Workup

  1. additionfilled microwave vessel
  2. customThe reaction solution is irradiated with microwaves for 30 min at 120° C. in the Biotage SmithSynthesizer
  3. filtrationthe mixture is filtered
  4. extractionThe filtrate is extracted three times with ethyl acetate
  5. washthe combined organic phases are washed 2× with water
  6. customdried
  7. customevaporated to dryness
  8. customThe oily residue is purified by means of RP-HPLC

Sources & evidence

ORD record
ord-2743e2f9d5c64b6da7d259413087769d
Source dataset
uspto-grants-2014_02
Patent number
US08648201B2

Reaction notes

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