Carbon Dioxide → N-[4-iodo-6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-2,2-dimethyl-propionamide

HRID 379373Notes

Reaction equation

HRID 379373 reaction equation
[CH3:1][C:2]([CH3:20])([CH3:19])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[CH:10][CH:11]=1)=[O:4].CN(C)CCN(C)C.C([Li])CCC.[I:34]I.C(=O)=O.O.O.O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>O1CCCC1.CCCCCC.O.C(OCC)C>[I:34][C:11]1[CH:10]=[C:9]([N:12]2[CH2:13][CH2:14][N:15]([CH3:18])[CH2:16][CH2:17]2)[N:8]=[CH:7][C:6]=1[NH:5][C:3](=[O:4])[C:2]([CH3:20])([CH3:19])[CH3:1]

Participants

11

Reactant 6

HCID 280Carbon DioxideHCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 61475Sodium Thiosulfate PentahydrateHCID 15887408N-(6-(4-Methylpiperazin-1-yl)pyridin-3-yl)pivalamideHCID 178418339Butyllithium

Product 1

HCID 15887409N-[4-iodo-6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-2,2-dimethyl-propionamideYield 42.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-30 °C

Procedure

A solution of 30 g (108 mmol) 2,2-dimethyl-N-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-propionamide and 58 ml (380 mmol) N,N,N′,N′-tetramethylethylenediamine under argon in 650 ml tetrahydrofuran was cooled in a dry ice bath to −78° C. Within lh, 239 ml (380 mmol) of a 1.6 N n-butyllithium solution in hexane were added dropwise. The reaction mixture was allowed to warm up to −30° C. overnight. After cooling again to −78° C., 43.6 g (170 mmol) iodine dissolved in 60 ml tetrahydrofuran were added dropwise during 15 min. The dry ice bath was replaced by an ice bath and a solution of 90 g (363 mmol) sodium thiosulfate pentahydrate in 250 ml water were added within 10 min when the temperature of the reaction mixture had reached 0° C. Then, 1000 ml diethyl ether were added and the organic layer was separated. The aqueous layer was extracted twice with 500 ml dichloromethane and the combined organic layers were dried (magnesium sulfate) and evaporated. Flash chromatography gave 18.5 g (42%) of the title compound as a light brown oil which crystallized upon standing at room temperature.

Workup

  1. temperatureAfter cooling again to −78° C.
  2. additionwere added dropwise during 15 min
  3. customhad reached 0° C
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted twice with 500 ml dichloromethane
  6. dry with materialthe combined organic layers were dried (magnesium sulfate)
  7. customevaporated

Sources & evidence

ORD record
ord-993880089ab6458bbf68a73d540e5791
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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