Potassium Carbonate → (S)-N-(1-(4-((1-Methyl-1H-pyrazol-4-yl) ethynyl)phenyl]ethyl}cyclopropane-carboxamide

HRID 76205

Reaction equation

HRID 76205 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([CH:7]=O)[CH:4]=[N:3]1.[C:9]([O-])([O-])=O.[K+].[K+].CC(C)(P(=O)([O-])[O-])C(=O)C=[N+]=[N-].I[C:28]1[CH:33]=[CH:32][C:31]([CH:34]([NH:36][C:37]([CH:39]2[CH2:41][CH2:40]2)=[O:38])[CH3:35])=[CH:30][CH:29]=1.CC(N)CC>CO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]#[C:9][C:28]2[CH:33]=[CH:32][C:31]([C@@H:34]([NH:36][C:37]([CH:39]3[CH2:41][CH2:40]3)=[O:38])[CH3:35])=[CH:30][CH:29]=2)[CH:4]=[N:3]1

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 24874Sec-ButylamineHCID 5731171-Methyl-1H-pyrazole-4-carbaldehydeHCID 66611166N-[1-(4-iodophenyl)ethyl]cyclopropanecarboxamideHCID 131731873Dimethyldiazo-2-oxopropylphosphonat

Product 1

HCID 66611617(S)-N-(1-(4-((1-Methyl-1H-pyrazol-4-yl) ethynyl)phenyl]ethyl}cyclopropane-carboxamide

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To 100 mg (0.91 mmol) 1-methyl-1H-pyrazole-4-carbaldehyde in 1.00 mL MeOH are added 289 mg (2.09 mmol) K2CO3 and finally dropwise 349 mg (1.82 mmol) dimethyldiazo-2-oxopropylphosphonat (in 2.0 mL MeOH).The reaction mixture is stirred at r.t. over night. The reaction is quenched by the addition of water and EtOAc. The organic layer is separated, dried with Na2SO4 and the solvent is removed in vacuo. To the residue is added 286 mg (0.91 mmol) cyclopropanecarboxylic acid [1-(4-iodo-phenyl)-ethyl]amide (I52.2), 63.7 mg (0.09 mmol) bis-(triphenylphosphin)-palladiumdichlorid, 2.00 mL 2-butylamine and 2.00 mL water. The reaction mixture is stirred at r.t. over night. The mixture is diluted with water and extracted with DCM. The organic layer is dried with Na2SO4 and the solvent is evaporated in vacuo. The residue is purified consecutively by column chromatography (silica gel, DCM/MeOH 98:2) and HPLC (MeOH/H2O/NH3).

Workup

  1. customThe reaction is quenched by the addition of water and EtOAc
  2. customThe organic layer is separated
  3. dry with materialdried with Na2SO4
  4. customthe solvent is removed in vacuo
  5. stirringThe reaction mixture is stirred at r.t. over night
  6. extractionextracted with DCM
  7. dry with materialThe organic layer is dried with Na2SO4
  8. customthe solvent is evaporated in vacuo
  9. customThe residue is purified consecutively by column chromatography (silica gel, DCM/MeOH 98:2) and HPLC (MeOH/H2O/NH3)

Sources & evidence

ORD record
ord-85efdbcbf919466babcf2722626b5c22
Source dataset
uspto-grants-2014_09
Patent number
US08835472B2

Linked notes

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