Potassium Sodium Tartrate → HCID 57504443, compound

HRID 1098067Notes

Reaction equation

HRID 1098067 reaction equation
[H-].[Na+].[N:3]1([CH2:7][C@H:8]([OH:18])[C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[O:10])[CH2:6][CH2:5][CH2:4]1.[Cl:19][C:20]1[C:21]([N:28]2[C:32]3=[N:33][CH:34]=[N:35][C:36](Cl)=[C:31]3[CH:30]=[N:29]2)=[C:22]([CH:25]=[CH:26][CH:27]=1)[C:23]#[N:24].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1>[N:3]1([CH2:7][C@H:8]([O:18][C:36]2[N:35]=[CH:34][N:33]=[C:32]3[N:28]([C:21]4[C:22]([C:23]#[N:24])=[CH:25][CH:26]=[CH:27][C:20]=4[Cl:19])[N:29]=[CH:30][C:31]=23)[C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[O:10])[CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 24758Sodium hydrideHCID 57504565HCID 57504565, compoundHCID 575045663-chloro-2-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzonitrile

Product 1

HCID 57504443HCID 57504443, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (116 mg, 2.90 mmol) was added to (S)-3-(azetidin-1-yl)-2-hydroxy-N-(pyridin-2-yl)propanamide (Intermediate BC1) (232 mg, 1.05 mmol) in anhydrous THF (50 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then a solution of 3-chloro-2-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzonitrile (Intermediate AH6) (280 mg, 0.97 mmol) in anhydrous THF (20 mL) was added dropwise over 1 minute. The mixture was stirred at 0° C. for 10 minutes and then allowed to warm to ambient temperature for 2 hours. It was then cooled to 0° C., 20% Rochelle salt (20 mL) added and the mixture stirred for 10 minutes. It was extracted with EtOAc (50 mL), the organic phase was washed with water (10 mL) and brine (20 mL), dried (MgSO4), filtered and evaporated. The residue was triturated with EtOAc (10 mL), filtered and the filtrates evaporated. The residue was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in EtOAc and further purified by preparative HPLC (Phenomenex Luna C18 100A column, 5μ silica, 21 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 1% formic acid) and MeCN as eluents to afford the product (100 mg, 22%).

Workup

  1. stirringThe mixture was stirred at 0° C. for 10 minutes
  2. temperatureto warm to ambient temperature for 2 hours
  3. temperatureIt was then cooled to 0° C.
  4. stirringthe mixture stirred for 10 minutes
  5. extractionIt was extracted with EtOAc (50 mL)
  6. washthe organic phase was washed with water (10 mL) and brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was triturated with EtOAc (10 mL)
  11. filtrationfiltered
  12. customthe filtrates evaporated
  13. customThe residue was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in EtOAc
  14. customfurther purified by preparative HPLC (Phenomenex Luna C18 100A column, 5μ silica, 21 mm diameter, 150 mm length)

Sources & evidence

ORD record
ord-42b1dbd77edb4899a481ad962f960b23
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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