Methanol → HCID 178480687, compound

HRID 334445Notes

Reaction equation

HRID 334445 reaction equation
B(Br)(Br)Br.[F:5][C:6]1[CH:7]=[C:8]([S:13][C:14]2[CH:15]=[C:16]3[C:24]([NH:25][C:26](=[O:47])[C:27]4[CH:32]=[CH:31][C:30]([N:33]5[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]5)=[CH:29][C:28]=4[NH:40][CH:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)=[N:23][NH:22][C:17]3=[N:18][C:19]=2[O:20]C)[CH:9]=[C:10]([F:12])[CH:11]=1.CO>ClCCl.ClCCCl>[F:5][C:6]1[CH:7]=[C:8]([S:13][C:14]2[CH:15]=[C:16]3[C:24]([NH:25][C:26](=[O:47])[C:27]4[CH:32]=[CH:31][C:30]([N:33]5[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]5)=[CH:29][C:28]=4[NH:40][CH:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)=[N:23][NH:22][C:17]3=[N:18][C:19]=2[OH:20])[CH:9]=[C:10]([F:12])[CH:11]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 178494016HCID 178494016, compound

Product 1

HCID 178480687HCID 178480687, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

443 μl (3 eq) of a solution of 1 M boron tribromide in dichloromethane is added to a solution of 90 mg (0.148 mmol) of N-(5-(3,5-difluorophenylthio)-6-methoxy-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide (example 18) in 4 ml of 1,2-dichloroethane at 0° C. The reaction medium is stirred at 60° C. for 3 hours and then cooled in an ice bath before adding methanol. The solvents are evaporated and the residue is redissolved in a mixture of methanol and ethyl acetate. The solid formed is filtered, redissolved in 3 ml of tetrahydrofuran and is added to 1 N soda solution. The reaction medium is stirred for 18 hours at room temperature. The pH of the solution is adjusted to 8-9 and the aqueous phase is extracted with ethyl acetate. The organic phase is dried on magnesium sulfate and the crude product is purified on a silica gel column (dichloromethane/methanol as eluent) to yield 21 mg (24%) of N-(5-(3,5-difluorophenylthio)-6-hydroxy-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide in the form of a yellow powder.

Workup

  1. temperaturecooled in an ice bath
  2. customThe solvents are evaporated
  3. dissolutionthe residue is redissolved in a mixture of methanol and ethyl acetate
  4. customThe solid formed
  5. filtrationis filtered
  6. dissolutionredissolved in 3 ml of tetrahydrofuran
  7. additionis added to 1 N soda solution
  8. stirringThe reaction medium is stirred for 18 hours at room temperature
  9. extractionthe aqueous phase is extracted with ethyl acetate
  10. customThe organic phase is dried on magnesium sulfate
  11. customthe crude product is purified on a silica gel column (dichloromethane/methanol as eluent)

Sources & evidence

ORD record
ord-d03a38c3015e461ab025f54c52b94ae3
Source dataset
uspto-grants-2014_11
Patent number
US08883821B2

Reaction notes

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