Toluene → HCID 57964978, compound

HRID 1931608Notes

Reaction equation

HRID 1931608 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][NH:15][C:16](OC(C)(C)C)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[NH2:32][C:33]1[N:38]=[C:37](Cl)[C:36](C=O)=[C:35]([Cl:42])[N:34]=1.C1(C)C=CC=CC=1>O1CCCC1.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:37]3=[N:38][C:33]([NH2:32])=[N:34][C:35]([Cl:42])=[C:36]3[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 1140TolueneHCID 81531DiisopropylethylamineHCID 2655462-Amino-4,6-dichloropyrimidine-5-carboxaldehydeHCID 20824232Tert-butyl 4-(2-(tert-butoxycarbonyl)hydrazinyl)piperidine-1-carboxylate2×

Product 1

HCID 57964978HCID 57964978, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

4-(tert-Butoxycarbonyl-hydrazino)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 15; 315 mg, 1 mmol) and diisopropylethylamine (2 mmol) were added to a solution of 2-amino-4,6-dichloro-pyrimidine-5-carbaldehyde (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 200 mg, 1 mmol) in tetrahydrofuran (3 mL). The mixture was warmed to room temperature, heated to reflux for 3 h, and then stirred overnight. The mixture was heated to reflux for a further 2 h and then cooled. Brine was added and the mixture was extracted three times with ethyl acetate. The combined organic extracts were dried (magnesium sulfate), filtered and evaporated to give a yellow foam. Toluene was added and the mixture was heated at 110° C. for 2 h. The mixture was cooled and purified by column chromatography (50% ethyl acetate/hexanes) to give 4-(6-amino-4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (315 mg, 69%) as a white powder.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 h
  3. temperatureThe mixture was heated
  4. temperatureto reflux for a further 2 h
  5. temperaturecooled
  6. extractionthe mixture was extracted three times with ethyl acetate
  7. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  8. filtrationfiltered
  9. customevaporated
  10. customto give a yellow foam
  11. temperaturethe mixture was heated at 110° C. for 2 h
  12. temperatureThe mixture was cooled
  13. custompurified by column chromatography (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-014826a49e604e13babd81e8c49368ea
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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