Sodium Nitrite → 6-[(6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl]-7-fluoroquinoline

HRID 456165Notes

Reaction equation

HRID 456165 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([NH:9][CH2:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[F:21])[N:17]=[CH:16][CH:15]=[CH:14]3)[C:5]([NH2:8])=[N:6][CH:7]=1.[N:22]([O-])=O.[Na+]>C(O)(=O)C.O>[Br:1][C:2]1[N:3]=[C:4]2[N:9]([CH2:10][C:11]3[CH:12]=[C:13]4[C:18](=[CH:19][C:20]=3[F:21])[N:17]=[CH:16][CH:15]=[CH:14]4)[N:22]=[N:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 23668193Sodium NitriteHCID 593417825-Bromo-N*3*-(7-fluoro-quinolin-6-ylmethyl)-pyrazine-2,3-diamine

Product 1

HCID 593418366-[(6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl]-7-fluoroquinolineYield 61%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a solution of 5-bromo-N*3*-(7-fluoro-quinolin-6-ylmethyl)-pyrazine-2,3-diamine (90 mg, 0.26 mmol) in acetic acid (4 mL), was added a solution of sodium nitrite (11.4 mg, 0.26 mmol) in water (1 mL) at once. After stirring at room temperature for 3 hour, the solvent was removed in vacuo and the residue was diluted with NaHCO3(aq.), extracted with DCM. The organic layer was washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography with (DCM:MeOH=50:1) to give the title compound as a yellow solid (57.0 mg, 61%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.03 (s, 1H), 8.94 (d, 1H), 8.40 (d, 1H), 8.08 (d, 1H), 7.84 (d, 1H), 7.55 (dd, 1H), 7.53 (dd, 1H), 6.21 (s, 2H). LCMS (method A): [MH]+=359/361, tR=2.23 min.

Workup

  1. customthe solvent was removed in vacuo
  2. additionthe residue was diluted with NaHCO3(aq.)
  3. extractionextracted with DCM
  4. washThe organic layer was washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography with (DCM:MeOH=50:1)

Sources & evidence

ORD record
ord-ac0e20bec8ce47cc87975312fc6cf4d4
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

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