2-Mercaptoethanol → 6-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-2-[(2-hydroxyethyl)thio]pyrimidine-4-carboxylic acid

HRID 2233914Notes

Reaction equation

HRID 2233914 reaction equation
Cl[C:2]1[NH:7][C:6]([N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19]([C:21]3[NH:22][C:23]([CH3:28])=[C:24]([Cl:27])[C:25]=3[Cl:26])=[O:20])[CH2:14][CH2:13]2)(C(OC)=O)[CH:5]=[CH:4][N:3]=1.[SH:29][CH2:30][CH2:31][OH:32].[C:33](=O)([O-:35])[O-:34].[K+].[K+]>CN(C=O)C.CCOC(C)=O.Cl>[Cl:26][C:25]1[C:24]([Cl:27])=[C:23]([CH3:28])[NH:22][C:21]=1[C:19]([NH:18][CH:15]1[CH2:14][CH2:13][N:12]([C:6]2[N:7]=[C:2]([S:29][CH2:30][CH2:31][OH:32])[N:3]=[C:4]([C:33]([OH:35])=[O:34])[CH:5]=2)[CH2:17][CH2:16]1)=[O:20]

Participants

7

Reactant 3

HCID 15672-MercaptoethanolHCID 11430Potassium CarbonateHCID 178499026HCID 178499026, compound

Product 1

HCID 685800786-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-2-[(2-hydroxyethyl)thio]pyrimidine-4-carboxylic acidYield 24.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of methyl 2-chloro-6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)pyrimidine-4-carboxylate (Example 6, 150 mg, 0.34 mmol), 2-mercaptoethanol (31 mg, 0.40 mmol) and potassium carbonate (139 mg, 1.01 mmol) in DMF (3 ml) were stirred at 65° C. under nitrogen for 3 hours. The mixture was cooled to room temperature and diluted with EtOAc (75 ml) and 1 N HCl (3 ml). The organic layer was separated, dried over Na2SO4, filtered and concentrated under vacuum. Purification of the residue by reversed-phase HPLC (water/acetonitrile gradient, 10-95%) gave 39 mg of the title compound.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customPurification of the residue by reversed-phase HPLC (water/acetonitrile gradient, 10-95%)

Sources & evidence

ORD record
ord-01a44b4e4353461cbf9c0471942bb24d
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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