Sodium Bicarbonate → HCID 135621936, compound

HRID 25439

Reaction equation

HRID 25439 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.C(=O)([O-])O.[Na+].I[C:26]1(C(OC(C)(C)C)=O)[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([N:35]([S:43]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[O:52][C:53]([F:56])([F:55])[F:54])(=[O:45])=[O:44])C(OC(C)(C)C)=O)[CH:33]=2)[N:28]=[N:27]1>CN(C)C=O>[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([NH:35][S:43]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[O:52][C:53]([F:54])([F:55])[F:56])(=[O:45])=[O:44])[CH:33]=2)[NH:28][N:27]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)HCID 22567356HCID 22567356, compound

Product 1

HCID 135621936HCID 135621936, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

N-[3-(1H-Indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxybenzenesulfonamide can be obtained in the following way: 213.3 mg N-tert-butoxycarbonylindole-2-boronic acid in dimer form and 243 μl of a saturated sodium hydrogencarbonate solution and then 63.4 mg of tetrakis(triphenylphosphine)palladium[0] are added to a solution of 150 mg of tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-trifluoromethoxybenzenesulfonylamino)indazolecarboxylate in 4.5 ml of dimethylformamide. The suspension is heated in the region of 120° C. for 18 hours. After cooling to a temperature in the region of 20° C., the catalyst is filtered through sintered glass with Celite® 535, and the filtrate is concentrated to dryness under reduced pressure in a rotary evaporator. The reaction crude is purified by preparative HPLC chromatography coupled to a mass detector (LC/MS, conditions A). The fractions containing the expected product are pooled and concentrated, and then the base is released from the trifluoroacetate salt by being taken up in 10 ml of dichloromethane and washed with 10 ml of a saturated sodium hydrogencarbonate solution. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. 60.5 mg of N-[3-(1H-indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxy-benzenesulfonamide are thus obtained in the form of a white solid melting at 172-174° C. (analytical LC/MS analysis: Tr=3.73 minutes; [M+H]+=473.07).

Workup

  1. temperatureAfter cooling to a temperature in the region of 20° C.
  2. filtrationthe catalyst is filtered through sintered glass with Celite® 535
  3. concentrationthe filtrate is concentrated to dryness under reduced pressure in a rotary evaporator
  4. customThe reaction crude
  5. customis purified by preparative HPLC chromatography
  6. additionThe fractions containing the expected product
  7. concentrationconcentrated
  8. washwashed with 10 ml of a saturated sodium hydrogencarbonate solution
  9. dry with materialThe organic phase is dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-4ecd565636464ee1a6ae4dacb0b0527b
Source dataset
uspto-grants-2005_02
Patent number
US06858638B2

Linked notes

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