1-Butanol → HCID 178511746, compound

HRID 1048806Notes

Reaction equation

HRID 1048806 reaction equation
C([N:3](CC)CC)C.[F:8][C:9]1[CH:10]=[C:11]([S:16][C:17]2C=[C:19]3[C:25]([NH:26][C:27](=[O:59])[C:28]4[CH:33]=[CH:32][C:31]([N:34]5[CH2:38][CH2:37][C@H:36]([NH:39]C(=O)C(F)(F)F)[CH2:35]5)=[CH:30][C:29]=4[N:46]([CH:53]4[CH2:58][CH2:57][O:56][CH2:55][CH2:54]4)C(=O)C(F)(F)F)=[N:24][NH:23][C:20]3=[N:21][CH:22]=2)[CH:12]=[C:13]([F:15])[CH:14]=1.C(O)CCC.C(=O)([O-])[O-].[K+].[K+]>CO>[NH2:39][C@H:36]1[CH2:37][CH2:38][N:34]([C:31]2[CH:32]=[CH:33][C:28]([C:27]([NH:26][C:25]3[C:19]4[C:20](=[N:21][CH:22]=[C:17]([S:16][C:11]5[CH:10]=[C:9]([F:8])[CH:14]=[C:13]([F:15])[CH:12]=5)[N:3]=4)[NH:23][N:24]=3)=[O:59])=[C:29]([NH:46][CH:53]3[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)[CH:30]=2)[CH2:35]1

Participants

6

Reactant 4

HCID 2631-ButanolHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 178522643HCID 178522643, compound

Product 1

HCID 178511746HCID 178511746, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

876 μl (20 eq) of triethylamine is added to a solution of 238 mg (0.314 mmol) of (S)—N-(5-(3,5-difluorophenylthio)-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)-4-(3-(2,2,2-trifluoroacetamido)pyrrolidin-1-yl)benzamide in 6 ml of methanol. The reaction medium is stirred at 65° C. for 4 hours. After returning to room temperature, 8 ml of n-butanol and 260 mg (6 eq) of potassium carbonate are added. The reaction medium is stirred at 80° C. for 24 hours. After returning to room temperature, the solvents are evaporated, water is added and the product is extracted with dichloromethane. The organic phase is washed with saturated sodium chloride solution, dried on magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (8:2 dichloromethane/methanol as eluent) to yield 87 mg (yield=49%) of (S)-4-(3-aminopyrrolidin-1-yl)-N-(5-(3,5-difluorophenylthio)-1H-pyrazolo[3,4-b]pyrazine-3-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide in the form of a brown powder.

Workup

  1. customAfter returning to room temperature
  2. stirringThe reaction medium is stirred at 80° C. for 24 hours
  3. customAfter returning to room temperature
  4. customthe solvents are evaporated
  5. additionwater is added
  6. extractionthe product is extracted with dichloromethane
  7. washThe organic phase is washed with saturated sodium chloride solution
  8. customdried on magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue is purified by silica gel chromatography (8:2 dichloromethane/methanol as eluent)

Sources & evidence

ORD record
ord-b7158626f47e45b097b07780430b70fd
Source dataset
uspto-grants-2016_07
Patent number
US09381195B2

Reaction notes

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