Dimethylformamide → 5,6-difluoro-N-(4-(3-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine

HRID 252652Notes

Reaction equation

HRID 252652 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[CH:2]=1.CN(C=O)C.[H-].[Na+].[F:15][C:16]1[C:48]([F:49])=[CH:47][C:19]2[NH:20][C:21]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][C:31]4[C:36]([C:37]5[CH:42]=[CH:41][N:40]=[C:39](S(C)(=O)=O)[N:38]=5)=[CH:35][CH:34]=[CH:33][N:32]=4)=[CH:26][CH:25]=3)=[N:22][C:18]=2[CH:17]=1>O.C(OCC)(=O)C>[F:15][C:16]1[C:48]([F:49])=[CH:47][C:19]2[NH:20][C:21]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][C:31]4[C:36]([C:37]5[CH:42]=[CH:41][N:40]=[C:39]([NH:7][C:3]6[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=6)[N:38]=5)=[CH:35][CH:34]=[CH:33][N:32]=4)=[CH:26][CH:25]=3)=[N:22][C:18]=2[CH:17]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 100093-AminopyridineHCID 24758Sodium hydrideHCID 668629535,6-difluoro-N-(4-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine

Product 1

HCID 589669675,6-difluoro-N-(4-(3-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A resealable reaction vial, under nitrogen, was charged with pyridin-3-amine (0.04 g, 42.50 mmol) and DMF (0.80 ml, 0.1 M). This was cooled to 0° C. and 60% wt in oil sodium hydride added (0.01 g, 42.50 mmol). The reaction mixture was stirred at 0° C. under a nitrogen atmosphere for 35 min. 5,6-Difluoro-N-(4-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine (0.04 g, 0.08 mmol) was added slowly to the mixture which was allowed to warm up to RT and stirred for 1 hr. The reaction mixture was heated to 60° C. and stirred for 1 hr. The reaction mixture was cooled to RT, then diluted with water and ethyl acetate. The layers were separated, the organic layer was dried over sodium sulfate and concentrated under reduced pressure to give oily residue, which was purified by silica prep plate (0.5% NH4OH/9.5% MeOH/Dichloromethane) followed by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA) to afford 5,6-difluoro-N-(4-(3-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine as a yellow solid. MS m/z=509.0 [M+H]+. Calc'd for C27H18F2N8O: 508.48.

Workup

  1. customA resealable reaction vial
  2. temperatureto warm up to RT
  3. stirringstirred for 1 hr
  4. temperatureThe reaction mixture was heated to 60° C.
  5. stirringstirred for 1 hr
  6. temperatureThe reaction mixture was cooled to RT
  7. customThe layers were separated
  8. dry with materialthe organic layer was dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto give oily residue, which
  11. customwas purified by silica prep plate (0.5% NH4OH/9.5% MeOH/Dichloromethane)

Sources & evidence

ORD record
ord-f37e1d1280f44c07af536b284371fa57
Source dataset
uspto-grants-2011_01
Patent number
US07868177B2

Reaction notes

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