Water → HCID 68998301, compound

HRID 2112753Notes

Reaction equation

HRID 2112753 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:38][CH2:37][C:11]2[N:12]=[C:13]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]([O:34]CC)=[O:33])[CH2:28][CH2:27]3)[N:14]=[C:15]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[Cl:25])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].O>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:38][CH2:37][C:11]2[N:12]=[C:13]([N:26]3[CH2:27][CH2:28][CH:29]([C:32]([OH:34])=[O:33])[CH2:30][CH2:31]3)[N:14]=[C:15]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[Cl:25])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 69002473HCID 69002473, compound

Product 1

HCID 68998301HCID 68998301, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

Ethyl 1-[6-tert-butoxycarbonyl-4-(2-chloro-4-fluorobenzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]piperidine-4-carboxylate (9.16 g, 16.1 mmol) prepared according to Process Step 3 was dissolved in ethanol (300 mL), and the solution was mixed with an aqueous sodium hydroxide solution (1 mol/L, 32 mL), followed by stirring at 65° C. for sixteen hours. After checking the completion of the reaction by thin layer chromatography, the reaction mixture was mixed with water and washed with diethyl ether. The aqueous layer was neutralized with diluted hydrochloric acid (1 mol/L, 35 mL), the precipitated crystals were collected by filtration and thereby yielded 1-[6-tert-butoxycarbonyl-4-(2-chloro-4-fluorobenzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]piperidine-4-carboxylic acid (3.94 g). The filtrate was extracted with dichloromethane, the organic layer was washed with brine, was dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was mixed with diethyl ether for crystallization. The precipitated crystals were collected by filtration and thereby yielded crystals of the target compound (1.07 g, 5.01 g in total with the above-mentioned crystals, in a yield of 62%).

Workup

  1. customthe completion of the reaction by thin layer chromatography
  2. washwashed with diethyl ether
  3. filtrationthe precipitated crystals were collected by filtration
  4. extractionThe filtrate was extracted with dichloromethane
  5. washthe organic layer was washed with brine
  6. dry with materialwas dried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off
  8. additionThe residue was mixed with diethyl ether for crystallization
  9. filtrationThe precipitated crystals were collected by filtration
  10. customyielded crystals of the target compound (1.07 g, 5.01 g in total with the above-mentioned crystals

Sources & evidence

ORD record
ord-0a009b28a8c94fb3a8e8cb705cda8b50
Source dataset
uspto-grants-2009_04
Patent number
US07524852B2

Reaction notes

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