Hydrochloric Acid → HCID 136059247, compound

HRID 336854Notes

Reaction equation

HRID 336854 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]([C:15]#[N:16])=[C:13]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=3[F:24])[N:12]=[C:11]3[NH:25][N:26]=[CH:27][C:10]=23)=[CH:5][CH:4]=1)#[N:2].[N-:28]=[N+:29]=[N-:30].[Na+].C([Sn](Cl)(CCCC)CCCC)CCC.Cl>CN(C=O)C>[N:2]1[NH:28][N:29]=[N:30][C:1]=1[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:14]([C:15]#[N:16])=[C:13]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=3[F:24])[N:12]=[C:11]3[NH:25][N:26]=[CH:27][C:10]=23)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 15096Tributyltin Chloride2×HCID 33557Sodium Azide2×HCID 136353007HCID 136353007, compound

Product 1

HCID 136059247HCID 136059247, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 100 mg (0.28 mmol) of 4-(4-cyanophenyl)-6-(2-fluoro-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile in 5 ml of anhydrous DMF are added 84 mg (1.12 mmol) of sodium azide and 305 μL (366 mg, 1.12 mmol) of tributyltin chloride. The mixture is heated to 130° C. under nitrogen for 8 h. Then 19 mg (0.28 mmol) of sodium azide and 77 μL (92 mg, 0.28 mmol) of tributyltin chloride are added, and the mixture is again heated to 130° C. for 48 h. After return to room temperature, the mixture is poured onto a water/ice mixture and acidified with a 6N HCl solution. The aqueous phase is extracted once with dichloromethane and twice with chloroform. The organic phase is washed with sodium chloride saturated solution, dried over sodium sulfate, filtered, and concentrated. The solid obtained is then purified by chromatography on silica (methanol gradient in dichloromethane: 15 to 25%) to give 0.032 g (29%) of 4-(4-(2H-tetrazole-5-yl)phenyl)-6-(2-fluoro-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile in the form of beige crystals.

Workup

  1. temperaturethe mixture is again heated to 130° C. for 48 h
  2. extractionThe aqueous phase is extracted once with dichloromethane and twice with chloroform
  3. washThe organic phase is washed with sodium chloride saturated solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe solid obtained
  8. customis then purified by chromatography on silica (methanol gradient in dichloromethane: 15 to 25%)

Sources & evidence

ORD record
ord-c5650e0cc4d849709a9a67c33c5e1080
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

Loading…