Stannous chloride dihydrate → 5-bromo-3-(4-fluorophenyl)-1H-indazole

HRID 1272779Notes

Reaction equation

HRID 1272779 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)=O.[N:18]([O-])=O.[Na+].O.O.[Sn](Cl)Cl>Cl.O1CCCC1.O>[Br:17][C:14]1[CH:13]=[C:3]2[C:2](=[CH:16][CH:15]=1)[NH:1][N:18]=[C:4]2[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1

Participants

7

Reactant 3

HCID 61436Stannous chloride dihydrateHCID 1359860(2-Amino-5-bromophenyl)(4-fluorophenyl)methanoneHCID 23668193Sodium Nitrite

Product 1

HCID 224802935-bromo-3-(4-fluorophenyl)-1H-indazoleYield 39.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-amino-5-bromo-4′-fluorobenzophenone (13.50 g, 45.9 mmol) in 6 N hydrochloride solution (400 mL) and tetrahydrofuran (500 mL) at −15° C. was slowly dropped a solution of sodium nitrite (4.12 g, 59.7 mmol) in water (20 mL). After stirring for 30 minutes in cold bath, to the reaction mixture was added a solution of tin(II) chloride dihydrate (28.48 g, 126 mmol) in concentrated hydrochloric acid (70 mL) dropwise. A white solid precipitated immediately. After 30 minutes, the white solid was filtered, dissolved in ethyl acetate, and washed with saturated sodium bicarbonate. The filtrate was neutralized with sodium hydroxide and extracted with dichloromethane. The ethyl acetate and dichloromethane layers were combined, dried over magnesium sulfate, and concentrated. Crystallization from ethyl acetate gave the title compound as a white solid (5.266 g). The mother liquor was then purified by chromatography (SiO2, 15–30% ethyl acetate/hexane) to provide another batch of the title compound (3.429 g, total 8.695 g, 65% yield). 1H NMR (CDCl3) δ 10.54 (br s, 1H), 8.11 (m, 1H), 7.87–7.92 (m, 2H), 7.50 (m, 1H), 7.34 (d, 1H), 7.20–7.26 (m, 2H); ES-MS (m/z) 293 [M+3]+, 291 [M+1]+.

Workup

  1. customA white solid precipitated immediately
  2. waitAfter 30 minutes
  3. filtrationthe white solid was filtered
  4. dissolutiondissolved in ethyl acetate
  5. washwashed with saturated sodium bicarbonate
  6. extractionextracted with dichloromethane
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customCrystallization from ethyl acetate

Sources & evidence

ORD record
ord-ae4ed30debd14ad88a331821a2335dbf
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

Loading…