Phosphorus oxychloride → HCID 86715511, compound

HRID 2284598Notes

Reaction equation

HRID 2284598 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[N:16][C:17]([CH2:20][NH:21][CH:22]=O)=[CH:18][CH:19]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:24].O=P(Cl)(Cl)Cl>C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]4[N:16]([CH:22]=[N:21][CH:20]=4)[CH:15]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:24]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 86715510HCID 86715510, compound

Product 1

HCID 86715511HCID 86715511, compoundYield 53.8%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

6-(2-(4-Fluoro-3-methylphenyl)pyridin-3-yl)imidazo[1,5-a]pyridine (Compound 269) can be prepared via the reactions shown in the first two steps of Scheme 20: (2′-(4-Fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methanamine (2.18 g) and formic acid (15 mL) were stirred and heated under nitrogen atmosphere at 100° C. After 72 h, the reaction mixture was concentrated and partitioned between CH2Cl2/aq. NaHCO3. Usual work-up and purification by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 50-100% EtOAC/hexanes as elutant) provided 630 mg of N-((2′-(4-fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methyl)formamide as an off white solid. N-((2′-(4-fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methyl)formamide (630 mg) and POCl3 (3 mL) were stirred and heated in benzene (20 mL) overnight at 75° C. The reaction mixture was cooled to room temperature and concentrated. Subsequently, ice/water solution was added to the crude residue followed by CH2Cl2 and aq. NaHCO3. Upon allowing the solution warm to room temperature, organic layer was separated, stirred over Na2SO4, filtered and concentrated. Purification of the crude residue by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 2-8% MeOH/CH2Cl2 as an eluting solvent) provided 320 mg of 6-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)imidazo[1,5-a]pyridine as an off-white solid.

Workup

  1. concentrationconcentrated
  2. additionSubsequently, ice/water solution was added to the crude residue
  3. temperaturewarm to room temperature
  4. customorganic layer was separated
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude residue by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 2-8% MeOH/CH2Cl2 as an eluting solvent)

Sources & evidence

ORD record
ord-128aa61bb20545338701b6f22638c5b8
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

Loading…