(6-fluoro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)(1-methyl-1H-imidazol-2-yl)methanol → 6-fluoro-2-(4-fluorophenyl)-3-((1-methyl-1H-imidazol-2-yl)methyl)imidazo[1,2-a]pyridine

HRID 455119Notes

Reaction equation

HRID 455119 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:18]([C:20]3[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=3)O)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:18][C:20]3[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:10]=2)[CH:7]=1

Participants

3

Reactant 1

HCID 67028697(6-fluoro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)(1-methyl-1H-imidazol-2-yl)methanol

Product 1

HCID 670290646-fluoro-2-(4-fluorophenyl)-3-((1-methyl-1H-imidazol-2-yl)methyl)imidazo[1,2-a]pyridineYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A Teflon-capped high-pressure glass bottle was charged with (6-fluoro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)(1-methyl-1H-imidazol-2-yl)methanol (2.2 g, 6.4 mmoles, 1.0 eq.), dry CH2Cl2 (60 ml) and solid P2I4 (7.3 g, 12.9 mmoles, 2.0 eq.). The bottle was flushed with N2 and heated at 40° C. for 60 hours. The reaction was quenched with NaHCO3 (200 ml, 1.0 M in water), extracted (3×200 ml CH2Cl2), the organic layer was dried with MgSO4 and concentrated on rotary evaporator. The crude residue was purified by flash chromatography (30%→70% gradient of 10% MeOH/90% EtOAc in hexanes on a 330 g silica gel column). The purified product was crystallized from hot EtOAc. Yield: 1.1 g (53%). Repeated crystallization provided additional 0.7 g (34%) having equal purity. (0.19 g, 53% yield). M/e+ 325 for C18H15F2N4 (M+H)+; 1H-NMR (400 MHz, CDCl3) δ 8.35 (d, J=1.8 Hz, 1H), 7.68 (dd, J=7.7, 5.5 Hz, 2H), 7.57 (dd, J=9.9, 5.1 Hz, 1H), 7.25 (d, J=1.1 Hz, 1H), 7.18 (t, J=8.4 Hz, 1H), 7.11 (t, J=7.7 Hz, 1H), 6.92 (s, 1H), 6.74 (s, 1H), 4.50 (s, 2H), 3.19 (s, 3H) ppm.

Workup

  1. customThe bottle was flushed with N2
  2. customThe reaction was quenched with NaHCO3 (200 ml, 1.0 M in water)
  3. extractionextracted (3×200 ml CH2Cl2)
  4. dry with materialthe organic layer was dried with MgSO4
  5. concentrationconcentrated on rotary evaporator
  6. customThe crude residue was purified by flash chromatography (30%→70% gradient of 10% MeOH/90% EtOAc in hexanes on a 330 g silica gel column)
  7. customThe purified product was crystallized from hot EtOAc
  8. customcrystallization
  9. customprovided additional 0.7 g (34%)

Sources & evidence

ORD record
ord-d39beade851548419a1715894f72e590
Source dataset
uspto-grants-2013_07
Patent number
US08497278B2

Reaction notes

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