Water → HCID 10064982, compound

HRID 497604Notes

Reaction equation

HRID 497604 reaction equation
F[B-](F)(F)F.[O:6]=[N+:7]=[O:8].[Br:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]([NH:19][C:20](=[O:24])[CH2:21][CH2:22][CH3:23])=[N:15][NH:16]2)=[CH:12][CH:11]=1.C(OCC)(=O)C.O>C(#N)C>[Br:9][C:10]1[C:18]([N+:7]([O-:8])=[O:6])=[C:17]2[C:13]([C:14]([NH:19][C:20](=[O:24])[CH2:21][CH2:22][CH3:23])=[N:15][NH:16]2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 10423871HCID 10423871, compoundHCID 11073463Nitronium tetrafluoroborate

Product 1

HCID 10064982HCID 10064982, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
3 °C

Procedure

235 mg of nitronium tetrafluoroborate are added in a single portion to 500 mg of N-[6-bromo-1H-indazol-3-yl]butanamide, described previously in Example 24, in 25 cm3 of acetonitrile, cooled to about 3° C. The mixture is maintained at about 3° C. for 1 hour and the resulting mixture is then allowed to return to about 19° C. over 14 hours. 15 cm3 of ethyl acetate and 15 cm3 of distilled water are added to the reaction medium. The medium is then evaporated under reduced pressure (2 kPa; 40° C.) and the residue is taken up in 20 cm3 of dichloromethane. The insoluble material is filtered off and washed with 20 cm3 of diisopropyl ether. The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with ethyl acetate/cyclohexane (30/70 by volume) and collecting 35 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 50° C.), 30 mg of N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide are thus obtained in the form of a white product melting at 248° C.

Workup

  1. temperatureThe mixture is maintained at about 3° C. for 1 hour
  2. customThe medium is then evaporated under reduced pressure (2 kPa; 40° C.)
  3. filtrationThe insoluble material is filtered off
  4. washwashed with 20 cm3 of diisopropyl ether
  5. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  6. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with ethyl acetate/cyclohexane (30/70 by volume)
  7. customcollecting 35 cm3 fractions
  8. additionThe fractions containing the expected product
  9. customevaporated under reduced pressure (2 kPa; 50° C.)
  10. dry with materialAfter drying (90 Pa; 50° C.), 30 mg of N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide

Sources & evidence

ORD record
ord-8240f3b300ac420daae76305fc2740b1
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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