Hydrochloric Acid → HCID 58919237, compound

HRID 539713Notes

Reaction equation

HRID 539713 reaction equation
[F:1][C:2]1[C:21]([NH:22][C:23]([NH:25][C:26]2[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=2)=[O:24])=[C:20]([F:33])[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14](C)(C)C)=[O:12])[CH2:7][CH2:6]1.Cl.ClC(OC)=O.CCN(CC)CC>CO.O1CCOCC1>[F:1][C:2]1[C:21]([NH:22][C:23]([NH:25][C:26]2[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=2)=[O:24])=[C:20]([F:33])[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH3:14])=[O:12])[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 58919238HCID 58919238, compound

Product 1

HCID 58919237HCID 58919237, compoundYield 38.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl 4-(2,4-difluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate (790 mg, 1.71 mmol, 1.0 equiv) in MeOH (5 mL) was added by syringe HCl (71 (4.0 M in dioxane, 4.5 mL, 17 mmol, 10 equiv) After 30 minutes, the reaction mixture was concentrated in vacuo. The resulting solid was then suspended in DCM (20 mL) and methyl chloroformate (158 μL, 2.05 mmol, 1.2 equiv) and Et3N (716 μL, 5.13 mmol, 3.0 equiv) were added by syringe. The reaction mixture was allowed to stir at room temperature for 1.5 h and then quenched by the addition of aq. satd. NaHCO3. The organic layer was separated, dried over sodium sulfate and purified by preparative thin layer chromatography (10% MeOH/DCM) to provide methyl 4-(2,4-difluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate (275 mg, 38%). LCMS m/z (APCI)=420.2 (M+H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customquenched by the addition of aq. satd
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. custompurified by preparative thin layer chromatography (10% MeOH/DCM)

Sources & evidence

ORD record
ord-cee7ddabfbb844a6ac6ca58943abcc8a
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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