Toluene → HCID 42643906, compound

HRID 1969112Notes

Reaction equation

HRID 1969112 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([CH:28]=[CH:29][N:30]=2)[CH:5]=[C:6]([C:8]2[C:9]([CH3:27])=[C:10]([NH:14][C:15](=[O:26])[C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=3)[CH:11]=[CH:12][CH:13]=2)[CH:7]=1.[CH:31]([N:34]([CH:37](C)C)CC)(C)[CH3:32].C(Cl)(Cl)=[O:41].C1(C)C=CC=CC=1>ClCCl>[C:22]([C:19]1[CH:20]=[CH:21][C:16]([C:15]([NH:14][C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([C:6]3[CH:7]=[C:2]([NH:1][C:37]([NH:34][CH2:31][CH3:32])=[O:41])[C:3]4[N:4]([CH:28]=[CH:29][N:30]=4)[CH:5]=3)[C:9]=2[CH3:27])=[O:26])=[CH:17][CH:18]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 1140TolueneHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 42643655HCID 42643655, compound

Product 1

HCID 42643906HCID 42643906, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To N-[3-(8-Amino-imidazo[1,2-a]pyridin-6-yl)-2-methyl-phenyl]-4-tert-butyl-benzamide (53 mg, 0.133 mmol) in dichloromethane (5 mL) at 0° C. was added diisopropylethylamine (60 μL, 2.5 eq) and the resulting mixture was stirred for 5 minutes. Then at 0° C. with stirring was added a 20% phosgene solution in toluene (84 μL, 1.2 eq) all at once, and the resulting solution was stirred at 0° C. for 5 minutes. Next, ethylamine(g) was bubbled through the solution for about 2 minutes. Additional phosgene solution (0.25 mL) was added at 0° C. and stirred an additional 5 minutes. Finally, ethylamine(g) was bubbled through the solution again for about 2 minutes. The reaction was quenched by adding ethyl acetate (35 mL) and water (25 mL). The layers were partitioned and then separated and the organic layer was further washed with brine (1×25 mL) and finally dried over magnesium sulfate, filtered and concentrated. This crude product was purified by Preparative Thin Layer Chromatography, eluting with 5% methanol in dichloromethane to give the title compound as a foamy solid (17 mg) ((M+H)+=470).

Workup

  1. stirringThen at 0° C. with stirring
  2. stirringwas stirred at 0° C. for 5 minutes
  3. customNext, ethylamine(g) was bubbled through the solution for about 2 minutes
  4. additionAdditional phosgene solution (0.25 mL) was added at 0° C.
  5. stirringstirred an additional 5 minutes
  6. customFinally, ethylamine(g) was bubbled through the solution again for about 2 minutes
  7. customThe reaction was quenched
  8. additionby adding ethyl acetate (35 mL) and water (25 mL)
  9. customThe layers were partitioned
  10. customseparated
  11. washthe organic layer was further washed with brine (1×25 mL)
  12. dry with materialfinally dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThis crude product was purified by Preparative Thin Layer Chromatography
  16. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-3691a0cef210401ea5c467bf3a6bc373
Source dataset
uspto-grants-2013_04
Patent number
US08426441B2

Reaction notes

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