Hydrogen Bromide → 3-Iodo-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine

HRID 558603Notes

Reaction equation

[F:1][C:2]([F:26])([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11](C(O)=O)=[C:7]2[CH:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[IH:27].Br.CC([O-])=O.[Na+].ICl.[O-]S([O-])=O.[Na+].[Na+]>C(O)(=O)C>[I:27][C:11]1[CH:10]=[N:9][N:8]2[C:3]([C:2]([F:26])([F:25])[F:1])=[CH:4][C:5]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)=[CH:6][C:7]=12

Participants

Conditions

Temperature: 23 °C

Procedure

A mixture of 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine-3-carboxylic acid (example C.22 step 8) (650 mg, 1.74 mmol) in acetic acid (20 mL) containing HI (57%, 200 uL) was refluxed for 2 days, but only 30% conversion. Added HBr (48%, 2 mL, 18 mmol) and continued refluxing for 2 h. Cooled to 23° C., added NaOAc (2.5 g, 30 mmol) and ICl (2M in HOAc, 6.1 mL, 12.2 mmol) and the mixture was stirred at 23° C. for 1 h. Added sat. Na2SO3-sol. to destroy excess ICl, diluted with water, filtered precipitate off, washed with water, dissolved in TBME, washed with sat. NaHCO3-sol. and brine, dried over Na2SO4. Removal of the solvent in vacuum left the title compound as a light yellow solid (740 mg, 93%; LC-MS shows mixture of bromide and iodide). MS (for iodide) (ISP) 456.2 [(M+H)+].

Workup

temperaturewas refluxed for 2 days
customto destroy excess ICl
additiondiluted with water
filtrationfiltered precipitate off,
washwashed with water
dissolutiondissolved in TBME
washwashed with sat. NaHCO3-sol
dry with materialand brine, dried over Na2SO4
customRemoval of the solvent in vacuum
waitleft the title compound as a light yellow solid (740 mg, 93%; LC-MS shows mixture of bromide and iodide)

Sources & evidence

ORD record: ord-f2de8d30e0424c5bbfc86195d438b8db
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063048B2

Reaction notes

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