Lithium Hydroxide → 1-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid

HRID 216270Notes

Reaction equation

HRID 216270 reaction equation
C[O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[C:15]([NH:17][CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])[N:14]=[C:13]([O:28][CH3:29])[N:12]=2)[CH2:7][CH2:6]1)=[O:4].[OH-].[Li+]>CO.C1COCC1>[Cl:27][C:21]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=1[CH2:19][CH2:18][NH:17][C:15]1[N:14]=[C:13]([O:28][CH3:29])[N:12]=[C:11]([N:8]2[CH2:7][CH2:6][CH:5]([C:3]([OH:4])=[O:2])[CH2:10][CH2:9]2)[CH:16]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 690694161-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 533178861-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acidYield 38.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester [70 mg, 0.16 mmol] and a 2 M solution of lithium hydroxide (1 mL, 2 mmol) in MeOH (1 mL) and THF (1 mL) is stirred at ambient temperature for 15 hours. The mixture is concentrated, and the residue is taken up with water, acidified to pH 2 with the addition of 10% HCl and extracted twice with EtOAc (20 mL). The organic extracts from the acidic layer are combined and dried over magnesium sulfate, filtered and concentrated to afford 1-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid [26 mg, 38%, Example 97] as a solid. LCMS RT=2.02 minutes, MS: 425 (M+H). IC50=7 nM

Workup

  1. concentrationThe mixture is concentrated
  2. additionacidified to pH 2 with the addition of 10% HCl
  3. extractionextracted twice with EtOAc (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-003803ead9d046739ee4e6a59b8fb182
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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