4-Toluenesulfonyl chloride → 2-{6-[Bis(tert-butoxycarbonyl)amino]-4-chloro-1-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}ethyl 4-methylbenzenesulfonate

HRID 1693266Notes

Reaction equation

HRID 1693266 reaction equation
C(N(CC)CC)C.[C:8]1([CH3:18])[CH:13]=[CH:12][C:11]([S:14](Cl)(=[O:16])=[O:15])=[CH:10][CH:9]=1.[C:19]([O:23][C:24]([N:26]([C:34]1[N:39]=[C:38]2[N:40]([CH2:46][C:47]3[C:52]([CH3:53])=[C:51]([O:54][CH3:55])[C:50]([CH3:56])=[CH:49][N:48]=3)[N:41]=[C:42]([CH2:43][CH2:44][OH:45])[C:37]2=[C:36]([Cl:57])[N:35]=1)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:25])([CH3:22])([CH3:21])[CH3:20]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:18][C:8]1[CH:13]=[CH:12][C:11]([S:14]([O:45][CH2:44][CH2:43][C:42]2[C:37]3[C:38](=[N:39][C:34]([N:26]([C:24]([O:23][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:25])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[N:35][C:36]=3[Cl:57])[N:40]([CH2:46][C:47]3[C:52]([CH3:53])=[C:51]([O:54][CH3:55])[C:50]([CH3:56])=[CH:49][N:48]=3)[N:41]=2)(=[O:16])=[O:15])=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 59311523di-tert-butyl{4-chloro-3-(2-hydroxyethyl)-1-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}imidodicarbonate

Product 1

HCID 593114662-{6-[Bis(tert-butoxycarbonyl)amino]-4-chloro-1-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}ethyl 4-methylbenzenesulfonateYield 91%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.048 mL), p-toluenesulfonyl chloride (43 mg) and 4-dimethylaminopyridine (0.7 mg) were added to a mixture composed of di-tert-butyl{4-chloro-3-(2-hydroxyethyl)-1-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}imidodicarbonate of 8) above (64 mg) and dehydrated dichloromethane (1 mL) under cooling in an ice bath. The ice bath was removed and the mixture was stirred for 12 hours. The reaction mixture was diluted with ethyl acetate and sequentially washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain the title compound (74 mg, 91%) as an amorphous substance.

Workup

  1. temperatureunder cooling in an ice bath
  2. customThe ice bath was removed
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washsequentially washed with water and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-631433f2ceac4770acc98b76d2e628b3
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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