Hydrogen Bromide → HCID 22319628, compound

HRID 497715Notes

Reaction equation

HRID 497715 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([F:21])[C:14]=1[N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[NH:11][N:10]=[C:9]2[NH:22][C:23](=[O:27])[CH2:24][CH2:25][CH3:26].[BrH:28]>O>[Br:28][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([F:21])[C:14]=1[N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[NH:11][N:10]=[C:9]2[NH:22][C:23](=[O:27])[CH2:24][CH2:25][CH3:26]

Participants

5

Reactant 3

HCID 260Hydrogen Bromide2×HCID 22319481HCID 22319481, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 22319628HCID 22319628, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

A solution of 213 mg of sodium nitrite in 9 cm3 of water is added dropwise to a suspension, cooled to 5° C., of 900 mg of N-(5-amino-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide, prepared as previously, in 9 cm3 of water and 0.94 cm3 of 48% hydrobromic acid, and the mixture is stirred at 0° C. This suspension is added portionwise to a refluxing solution of 482 mg of cuprous bromide, 4.5 cm3 of water and 4.5 cm3 of 48% hydrobromic acid. Refluxing is continued for 45 minutes and the reaction medium is then filtered through a sinter funnel, dissolved in 75 cm3 of tetrahydrofuran and purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 15-40 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.) and the residue is taken up in 10 cm3 of ethyl acetate, filtered off and washed with 2×5 cm3 of ethyl acetate and with 20 cm3 of diisopropyl ether. After filtration and drying (90 Pa; 45° C.), 60 mg of N-(5-bromo-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide are obtained in the form of white crystals melting at 240° C.

Workup

  1. temperatureRefluxing
  2. filtrationthe reaction medium is then filtered through a sinter funnel
  3. dissolutiondissolved in 75 cm3 of tetrahydrofuran
  4. custompurified by chromatography under an argon pressure of 50 kPa
  5. washon a column of silica gel (particle size 15-40 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
  6. additionThe fractions containing the expected product
  7. customevaporated under reduced pressure (2 kPa; 50° C.)
  8. filtrationfiltered off
  9. washwashed with 2×5 cm3 of ethyl acetate and with 20 cm3 of diisopropyl ether
  10. filtrationAfter filtration
  11. dry with materialdrying (90 Pa; 45° C.), 60 mg of N-(5-bromo-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide

Sources & evidence

ORD record
ord-446df0df360042ed86c763d3bfe51a42
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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