Hydrochloric Acid → HCID 23660490, compound

HRID 539714Notes

Reaction equation

HRID 539714 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])=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1.Cl.[CH3:34][S:35](Cl)(=[O:37])=[O:36].CCN(C(C)C)C(C)C>CO>[F:1][C:2]1[C:3]([CH2:4][N:5]2[CH2:10][CH2:9][N:8]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:7][CH2:6]2)=[CH:18][CH:19]=[CH:20][C:21]=1[NH:22][C:23]([NH:25][C:26]1[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=1)=[O:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 57597090HCID 57597090, compound

Product 1

HCID 23660490HCID 23660490, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate (1.3 g, 2.9 mmol, 1.0 equiv) in MeOH (10 mL) was added by syringe HCl (4.0 M in dioxane, 10 mL, 40 mmol, 13.8 equiv) After 30 minutes, the reaction mixture was concentrated in vacuo. The resulting solid was then suspended in THF (10 mL) and methanesulfonyl chloride (220 μL, 2.9 mmol, 1.0 equiv) and DIPEA (2.0 mL, 11.5 mmol, 4.0 equiv) were added by syringe. The reaction mixture was allowed to stir at room temperature for 0.5 h and then quenched by the addition of aq. satd. NaHCO3. The organic layer was separated, dried over sodium sulfate and purified by flash chromatography on silica gel (1%-10% MeOH/DCM) to provide 1-(2-fluoro-3-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)-3-(6-methylpyridin-3-yl)urea (930 mg, 76%). LCMS m/z (APCI)=422.2 (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 flash chromatography on silica gel (1%-10% MeOH/DCM)

Sources & evidence

ORD record
ord-724854de4ac94d6ebeccdb9d91c89a08
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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