Phosphorus oxychloride → 8-Fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH2:11][NH:12][CH:13]=O)=[N:6][C:5]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[F:23].P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([F:10])[C:7]2[N:6]([CH:13]=[N:12][CH:11]=2)[C:5]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[F:23])=[O:24]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
To a suspension of 5-fluoro-2-(2-fluoro-4-iodo-phenylamino)-6-formylaminomethyl-nicotinic acid methyl ester (2.7 g, 6.2 mmol) in toluene (20 mL) was added phosphorous oxychloride (1.1 mL, 12.2 mmol). The reaction mixture was heated at 95° C. for 30 minutes. The reaction mixture was cooled to room temperature and then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with water followed by a saturated aqueous solution of sodium bicarbonate, then brine. The organic phase was isolated, dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 50%, ethyl acetate in hexane) to afford the title compound as a yellow solid (1.0 g, 39%). LCMS (method B): RT=3.97 min, [M+H]+=430.
Workup
- temperatureThe reaction mixture was cooled to room temperature
- concentrationconcentrated in vacuo
- dissolutionThe resultant residue was dissolved in ethyl acetate
- washwashed with water
- customThe organic phase was isolated
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-241c7be536634507bf9f775ba8d5f6a8
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07923456B2
Reaction notes
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